paragraph_index int64 | sec string | p_has_citation int64 | cites string | citeids list | pmid int64 | cited_id string | sentences string | all_sent_cites list | sent_len int64 | sentence_batch_index int64 | sent_has_citation float64 | qc_fail bool | cited_sentence string | cites_in_sentence list | cln_sentence string | is_cap bool | is_alpha bool | ends_wp bool | cit_qc bool | lgtm bool | __index_level_0__ int64 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
2 | DISCUSSION | 0 | null | null | 17,182,632 | pmid-15205459|pmid-8390996 | Hepatotoxicity was chemistry-, sequence- and design-dependent, as it was only observed with LNA containing ASOs, and the onset occurred at slightly different dose levels for different compounds. | null | 194 | 200 | 0 | false | null | null | Hepatotoxicity was chemistry-, sequence- and design-dependent, as it was only observed with LNA containing ASOs, and the onset occurred at slightly different dose levels for different compounds. | true | true | true | true | true | 37 |
2 | DISCUSSION | 0 | null | null | 17,182,632 | pmid-15205459|pmid-8390996 | The fact that the MOE ASOs in some cases (compare 2a with 2b, and 6 with 7b and 8b) produced similar reductions in target RNA without producing observable toxicity suggest that the toxicity is not secondary to reduction in target gene expression. | null | 246 | 201 | 0 | false | null | null | The fact that the MOE ASOs in some cases (compare 2a with 2b, and 6 with 7b and 8b) produced similar reductions in target RNA without producing observable toxicity suggest that the toxicity is not secondary to reduction in target gene expression. | true | true | true | true | true | 37 |
2 | DISCUSSION | 0 | null | null | 17,182,632 | pmid-15205459|pmid-8390996 | This is further supported by the observation of severe hepatotoxicity with control 5b, which has >3 mismatches to all known mouse sequences. | null | 140 | 202 | 0 | false | null | null | This is further supported by the observation of severe hepatotoxicity with control 5b, which has >3 mismatches to all known mouse sequences. | true | true | true | true | true | 37 |
2 | DISCUSSION | 0 | null | null | 17,182,632 | pmid-15205459|pmid-8390996 | Hepatotoxicity also seemed to be the most severe for the more potent LNA ASO designs regardless of target (see 4b, mismatch 5b, 7b and 10b). | null | 140 | 203 | 0 | false | null | null | Hepatotoxicity also seemed to be the most severe for the more potent LNA ASO designs regardless of target (see 4b, mismatch 5b, 7b and 10b). | true | true | true | true | true | 37 |
2 | DISCUSSION | 0 | null | null | 17,182,632 | pmid-15205459|pmid-8390996 | Thus, therapeutic index was not improved, and was likely decreased relative to the MOE ASOs. | null | 92 | 204 | 0 | false | null | null | Thus, therapeutic index was not improved, and was likely decreased relative to the MOE ASOs. | true | true | true | true | true | 37 |
3 | DISCUSSION | 1 | 42 | [
"b42",
"b43",
"b44"
] | 17,182,632 | pmid-14963330|pmid-12667443|pmid-10749144 | The hepatotoxicity was evident from the observation of multiple parameters, including histopathological evaluation of liver tissue upon necropsy as well as large increases in plasma levels of aminotransferases (ALT and AST). | [
"42",
"43",
"44"
] | 224 | 205 | 0 | false | The hepatotoxicity was evident from the observation of multiple parameters, including histopathological evaluation of liver tissue upon necropsy as well as large increases in plasma levels of aminotransferases (ALT and AST). | [] | The hepatotoxicity was evident from the observation of multiple parameters, including histopathological evaluation of liver tissue upon necropsy as well as large increases in plasma levels of aminotransferases (ALT and AST). | true | true | true | true | true | 38 |
3 | DISCUSSION | 1 | 42 | [
"b42",
"b43",
"b44"
] | 17,182,632 | pmid-14963330|pmid-12667443|pmid-10749144 | Furthermore, the toxicity was commonly accompanied by large increases in liver and/or spleen weights, likely as a consequence arising from a response to hepatic injury induced by the LNA ASOs. | [
"42",
"43",
"44"
] | 192 | 206 | 0 | false | Furthermore, the toxicity was commonly accompanied by large increases in liver and/or spleen weights, likely as a consequence arising from a response to hepatic injury induced by the LNA ASOs. | [] | Furthermore, the toxicity was commonly accompanied by large increases in liver and/or spleen weights, likely as a consequence arising from a response to hepatic injury induced by the LNA ASOs. | true | true | true | true | true | 38 |
3 | DISCUSSION | 1 | 42 | [
"b42",
"b43",
"b44"
] | 17,182,632 | pmid-14963330|pmid-12667443|pmid-10749144 | In several cases, the toxicity was severe enough to cause extensive weight loss in the animals. | [
"42",
"43",
"44"
] | 95 | 207 | 0 | false | In several cases, the toxicity was severe enough to cause extensive weight loss in the animals. | [] | In several cases, the toxicity was severe enough to cause extensive weight loss in the animals. | true | true | true | true | true | 38 |
3 | DISCUSSION | 1 | 42 | [
"b42",
"b43",
"b44"
] | 17,182,632 | pmid-14963330|pmid-12667443|pmid-10749144 | Histology data clearly demonstrated both LNA oligonucleotide-indiced liver necrosis and activation of apoptosis pathways, as evidenced by H&E staining, as well as cleaved caspase 3, increased Bax expression and increased expression of the M30 neo-epitope. | [
"42",
"43",
"44"
] | 255 | 208 | 0 | false | Histology data clearly demonstrated both LNA oligonucleotide-indiced liver necrosis and activation of apoptosis pathways, as evidenced by H&E staining, as well as cleaved caspase 3, increased Bax expression and increased expression of the M30 neo-epitope. | [] | Histology data clearly demonstrated both LNA oligonucleotide-indiced liver necrosis and activation of apoptosis pathways, as evidenced by H&E staining, as well as cleaved caspase 3, increased Bax expression and increased expression of the M30 neo-epitope. | true | true | true | true | true | 38 |
3 | DISCUSSION | 1 | 42 | [
"b42",
"b43",
"b44"
] | 17,182,632 | pmid-14963330|pmid-12667443|pmid-10749144 | The upregulation of the pro-apoptotic protein Bax suggests involvement of the p53-mediated apoptosis pathway, as Bax is a key response gene to p53 activation (42,43). | [
"42",
"43",
"44"
] | 166 | 209 | 0 | false | The upregulation of the pro-apoptotic protein Bax suggests involvement of the p53-mediated apoptosis pathway, as Bax is a key response gene to p53 activation. | [
"42,43"
] | The upregulation of the pro-apoptotic protein Bax suggests involvement of the p53-mediated apoptosis pathway, as Bax is a key response gene to p53 activation. | true | true | true | true | true | 38 |
3 | DISCUSSION | 1 | 44 | [
"b42",
"b43",
"b44"
] | 17,182,632 | pmid-14963330|pmid-12667443|pmid-10749144 | Furthermore, GADD45β, a key downstream target gene of p53 during DNA damage and repair process (44), was highly up-regulated in the injured hepatocytes. | [
"42",
"43",
"44"
] | 152 | 210 | 1 | false | Furthermore, GADD45β, a key downstream target gene of p53 during DNA damage and repair process, was highly up-regulated in the injured hepatocytes. | [
"44"
] | Furthermore, GADD45β, a key downstream target gene of p53 during DNA damage and repair process, was highly up-regulated in the injured hepatocytes. | true | true | true | true | true | 38 |
3 | DISCUSSION | 1 | 42 | [
"b42",
"b43",
"b44"
] | 17,182,632 | pmid-14963330|pmid-12667443|pmid-10749144 | GADD45β appears to help protect cells against programmed cell death through blocking the c-jun N-terminal kinase cascade, and is probably induced in response to cellular damage. | [
"42",
"43",
"44"
] | 177 | 211 | 0 | false | GADD45β appears to help protect cells against programmed cell death through blocking the c-jun N-terminal kinase cascade, and is probably induced in response to cellular damage. | [] | GADD45β appears to help protect cells against programmed cell death through blocking the c-jun N-terminal kinase cascade, and is probably induced in response to cellular damage. | true | true | true | true | true | 38 |
4 | DISCUSSION | 1 | 45 | [
"b45",
"b8"
] | 17,182,632 | NA|pmid-10360355|pmid-9880552|NA|pmid-11181921|pmid-14570775|pmid-10932156|pmid-11160622|pmid-11160622|pmid-15716585|pmid-17030687|pmid-17030687|pmid-12438559|pmid-15625915|pmid-10360355 | It is unclear why LNA oligonucleotides cause this level of hepatotoxicity though the corresponding MOE oligonucleotides do not. | [
"45",
"8"
] | 127 | 212 | 0 | false | It is unclear why LNA oligonucleotides cause this level of hepatotoxicity though the corresponding MOE oligonucleotides do not. | [] | It is unclear why LNA oligonucleotides cause this level of hepatotoxicity though the corresponding MOE oligonucleotides do not. | true | true | true | true | true | 39 |
4 | DISCUSSION | 1 | 45 | [
"b45",
"b8"
] | 17,182,632 | NA|pmid-10360355|pmid-9880552|NA|pmid-11181921|pmid-14570775|pmid-10932156|pmid-11160622|pmid-11160622|pmid-15716585|pmid-17030687|pmid-17030687|pmid-12438559|pmid-15625915|pmid-10360355 | One possibility is that antisense effects on genes partially complementary to the hepatotoxic ASOs are playing a role in the toxicity, as LNA ASOs have been shown to decrease the selectivity for a perfectly complementary target relative to the corresponding MOE ASOs (45). | [
"45",
"8"
] | 272 | 213 | 1 | false | One possibility is that antisense effects on genes partially complementary to the hepatotoxic ASOs are playing a role in the toxicity, as LNA ASOs have been shown to decrease the selectivity for a perfectly complementary target relative to the corresponding MOE ASOs. | [
"45"
] | One possibility is that antisense effects on genes partially complementary to the hepatotoxic ASOs are playing a role in the toxicity, as LNA ASOs have been shown to decrease the selectivity for a perfectly complementary target relative to the corresponding MOE ASOs. | true | true | true | true | true | 39 |
4 | DISCUSSION | 1 | 45 | [
"b45",
"b8"
] | 17,182,632 | NA|pmid-10360355|pmid-9880552|NA|pmid-11181921|pmid-14570775|pmid-10932156|pmid-11160622|pmid-11160622|pmid-15716585|pmid-17030687|pmid-17030687|pmid-12438559|pmid-15625915|pmid-10360355 | However, this seems unlikely because multiple unrelated LNA sequences cause similar toxicities. | [
"45",
"8"
] | 95 | 214 | 0 | false | However, this seems unlikely because multiple unrelated LNA sequences cause similar toxicities. | [] | However, this seems unlikely because multiple unrelated LNA sequences cause similar toxicities. | true | true | true | true | true | 39 |
4 | DISCUSSION | 1 | 45 | [
"b45",
"b8"
] | 17,182,632 | NA|pmid-10360355|pmid-9880552|NA|pmid-11181921|pmid-14570775|pmid-10932156|pmid-11160622|pmid-11160622|pmid-15716585|pmid-17030687|pmid-17030687|pmid-12438559|pmid-15625915|pmid-10360355 | All oligonucleotides were prepared and purified in the same laboratory using the identical methods. | [
"45",
"8"
] | 99 | 215 | 0 | false | All oligonucleotides were prepared and purified in the same laboratory using the identical methods. | [] | All oligonucleotides were prepared and purified in the same laboratory using the identical methods. | true | true | true | true | true | 39 |
4 | DISCUSSION | 1 | 45 | [
"b45",
"b8"
] | 17,182,632 | NA|pmid-10360355|pmid-9880552|NA|pmid-11181921|pmid-14570775|pmid-10932156|pmid-11160622|pmid-11160622|pmid-15716585|pmid-17030687|pmid-17030687|pmid-12438559|pmid-15625915|pmid-10360355 | The impurity profiles of LNA and MOE ASOs were nearly identical, and contained only the expected impurities resulting from PS oligonucleotide synthesis (PO, N-1, etc. | [
"45",
"8"
] | 166 | 216 | 0 | false | The impurity profiles of LNA and MOE ASOs were nearly identical, and contained only the expected impurities resulting from PS oligonucleotide synthesis (PO, N-1, etc. | [] | The impurity profiles of LNA and MOE ASOs were nearly identical, and contained only the expected impurities resulting from PS oligonucleotide synthesis (PO, N-1, etc. | true | true | true | true | true | 39 |
4 | DISCUSSION | 1 | 45 | [
"b45",
"b8"
] | 17,182,632 | NA|pmid-10360355|pmid-9880552|NA|pmid-11181921|pmid-14570775|pmid-10932156|pmid-11160622|pmid-11160622|pmid-15716585|pmid-17030687|pmid-17030687|pmid-12438559|pmid-15625915|pmid-10360355 | This makes it extremely unlikely that the toxicity is due to impurities resulting from LNA, but not MOE oligonucleotide synthesis. | [
"45",
"8"
] | 130 | 217 | 0 | false | This makes it extremely unlikely that the toxicity is due to impurities resulting from LNA, but not MOE oligonucleotide synthesis. | [] | This makes it extremely unlikely that the toxicity is due to impurities resulting from LNA, but not MOE oligonucleotide synthesis. | true | true | true | true | true | 39 |
4 | DISCUSSION | 1 | 45 | [
"b45",
"b8"
] | 17,182,632 | NA|pmid-10360355|pmid-9880552|NA|pmid-11181921|pmid-14570775|pmid-10932156|pmid-11160622|pmid-11160622|pmid-15716585|pmid-17030687|pmid-17030687|pmid-12438559|pmid-15625915|pmid-10360355 | Additionally, since the metabolically unstable PO containing ASO 11b (which should be metabolized in vivo to LNA nucleosides and nucleotides) was non-toxic, it is not likely that the toxicity is due to the LNA monomers. | [
"45",
"8"
] | 219 | 218 | 0 | false | Additionally, since the metabolically unstable PO containing ASO 11b (which should be metabolized in vivo to LNA nucleosides and nucleotides) was non-toxic, it is not likely that the toxicity is due to the LNA monomers. | [] | Additionally, since the metabolically unstable PO containing ASO 11b (which should be metabolized in vivo to LNA nucleosides and nucleotides) was non-toxic, it is not likely that the toxicity is due to the LNA monomers. | true | true | true | true | true | 39 |
4 | DISCUSSION | 1 | 45 | [
"b45",
"b8"
] | 17,182,632 | NA|pmid-10360355|pmid-9880552|NA|pmid-11181921|pmid-14570775|pmid-10932156|pmid-11160622|pmid-11160622|pmid-15716585|pmid-17030687|pmid-17030687|pmid-12438559|pmid-15625915|pmid-10360355 | This suggests that the intact LNA containing PS oligonucleotides are responsible for the observed toxicity. | [
"45",
"8"
] | 107 | 219 | 0 | false | This suggests that the intact LNA containing PS oligonucleotides are responsible for the observed toxicity. | [] | This suggests that the intact LNA containing PS oligonucleotides are responsible for the observed toxicity. | true | true | true | true | true | 39 |
4 | DISCUSSION | 1 | 45 | [
"b45",
"b8"
] | 17,182,632 | NA|pmid-10360355|pmid-9880552|NA|pmid-11181921|pmid-14570775|pmid-10932156|pmid-11160622|pmid-11160622|pmid-15716585|pmid-17030687|pmid-17030687|pmid-12438559|pmid-15625915|pmid-10360355 | There are distinct structural differences between MOE and LNA which may allow LNA containing oligonucleotides to selectively effect hepatotoxicity. | [
"45",
"8"
] | 147 | 220 | 0 | false | There are distinct structural differences between MOE and LNA which may allow LNA containing oligonucleotides to selectively effect hepatotoxicity. | [] | There are distinct structural differences between MOE and LNA which may allow LNA containing oligonucleotides to selectively effect hepatotoxicity. | true | true | true | true | true | 39 |
4 | DISCUSSION | 1 | 8 | [
"b45",
"b8"
] | 17,182,632 | NA|pmid-10360355|pmid-9880552|NA|pmid-11181921|pmid-14570775|pmid-10932156|pmid-11160622|pmid-11160622|pmid-15716585|pmid-17030687|pmid-17030687|pmid-12438559|pmid-15625915|pmid-10360355 | Perhaps importantly, the rigid acyclic 2′-methoxyethyl side chain of MOE protects the corresponding 3′-phosphorothioate linkage from interactions via increased steric bulk and hydration (8), relative to the compact and more hydrophobic cyclic structure of LNA. | [
"45",
"8"
] | 260 | 221 | 1 | false | Perhaps importantly, the rigid acyclic 2′-methoxyethyl side chain of MOE protects the corresponding 3′-phosphorothioate linkage from interactions via increased steric bulk and hydration, relative to the compact and more hydrophobic cyclic structure of LNA. | [
"8"
] | Perhaps importantly, the rigid acyclic 2′-methoxyethyl side chain of MOE protects the corresponding 3′-phosphorothioate linkage from interactions via increased steric bulk and hydration, relative to the compact and more hydrophobic cyclic structure of LNA. | true | true | true | true | true | 39 |
4 | DISCUSSION | 1 | 45 | [
"b45",
"b8"
] | 17,182,632 | NA|pmid-10360355|pmid-9880552|NA|pmid-11181921|pmid-14570775|pmid-10932156|pmid-11160622|pmid-11160622|pmid-15716585|pmid-17030687|pmid-17030687|pmid-12438559|pmid-15625915|pmid-10360355 | This could cause selective binding affinity differences between MOE and LNA oligonucleotides for as yet unknown macromolecular binding partners, and/or result in differential compartmentalization of the two classes of oligonucleotides within liver tissue. | [
"45",
"8"
] | 255 | 222 | 0 | false | This could cause selective binding affinity differences between MOE and LNA oligonucleotides for as yet unknown macromolecular binding partners, and/or result in differential compartmentalization of the two classes of oligonucleotides within liver tissue. | [] | This could cause selective binding affinity differences between MOE and LNA oligonucleotides for as yet unknown macromolecular binding partners, and/or result in differential compartmentalization of the two classes of oligonucleotides within liver tissue. | true | true | true | true | true | 39 |
5 | DISCUSSION | 1 | 41 | [
"b41",
"b46",
"b47",
"b48"
] | 17,182,632 | NA|NA|NA|NA|NA|pmid-16717090|pmid-11555640|pmid-11032824|pmid-8995434 | The mild hepatotoxicity induced 4 days after a single administration of LNA ASO 4b occurred concurrently with apoptosis and activation of Bax and caspase 3 in hepatocytes as evidenced by histopathological evaluation. | [
"41",
"46",
"47",
"48"
] | 216 | 223 | 0 | false | The mild hepatotoxicity induced 4 days after a single administration of LNA ASO 4b occurred concurrently with apoptosis and activation of Bax and caspase 3 in hepatocytes as evidenced by histopathological evaluation. | [] | The mild hepatotoxicity induced 4 days after a single administration of LNA ASO 4b occurred concurrently with apoptosis and activation of Bax and caspase 3 in hepatocytes as evidenced by histopathological evaluation. | true | true | true | true | true | 40 |
5 | DISCUSSION | 1 | 41 | [
"b41",
"b46",
"b47",
"b48"
] | 17,182,632 | NA|NA|NA|NA|NA|pmid-16717090|pmid-11555640|pmid-11032824|pmid-8995434 | Furthermore, an increase in p-eIF2α was observed to coincide with the onset of toxicity. | [
"41",
"46",
"47",
"48"
] | 88 | 224 | 0 | false | Furthermore, an increase in p-eIF2α was observed to coincide with the onset of toxicity. | [] | Furthermore, an increase in p-eIF2α was observed to coincide with the onset of toxicity. | true | true | true | true | true | 40 |
5 | DISCUSSION | 1 | 41 | [
"b41",
"b46",
"b47",
"b48"
] | 17,182,632 | NA|NA|NA|NA|NA|pmid-16717090|pmid-11555640|pmid-11032824|pmid-8995434 | Phosphorylated eIF2α inhibits translation initiation, and has been shown to mediate apoptosis, possibly by preventing the synthesis of short lived anti-apoptotic factors (41,46). | [
"41",
"46",
"47",
"48"
] | 178 | 225 | 0 | false | Phosphorylated eIF2α inhibits translation initiation, and has been shown to mediate apoptosis, possibly by preventing the synthesis of short lived anti-apoptotic factors. | [
"41,46"
] | Phosphorylated eIF2α inhibits translation initiation, and has been shown to mediate apoptosis, possibly by preventing the synthesis of short lived anti-apoptotic factors. | true | true | true | true | true | 40 |
5 | DISCUSSION | 1 | 41 | [
"b41",
"b46",
"b47",
"b48"
] | 17,182,632 | NA|NA|NA|NA|NA|pmid-16717090|pmid-11555640|pmid-11032824|pmid-8995434 | There are four known kinases which phosphorylate eIF2α: PKR, which is activated by binding of double stranded RNA (dsRNA); GCN2, which is activated by amino acid deprivation; HRI, which is activated by low heme levels; and PERK, which responds to stress in the endoplasmic reticulum. | [
"41",
"46",
"47",
"48"
] | 283 | 226 | 0 | false | There are four known kinases which phosphorylate eIF2α: PKR, which is activated by binding of double stranded RNA (dsRNA); GCN2, which is activated by amino acid deprivation; HRI, which is activated by low heme levels; and PERK, which responds to stress in the endoplasmic reticulum. | [] | There are four known kinases which phosphorylate eIF2α: PKR, which is activated by binding of double stranded RNA (dsRNA); GCN2, which is activated by amino acid deprivation; HRI, which is activated by low heme levels; and PERK, which responds to stress in the endoplasmic reticulum. | true | true | true | true | true | 40 |
5 | DISCUSSION | 1 | 41 | [
"b41",
"b46",
"b47",
"b48"
] | 17,182,632 | NA|NA|NA|NA|NA|pmid-16717090|pmid-11555640|pmid-11032824|pmid-8995434 | It is unclear from our data how treatment with hepatotoxic LNA oligonucleotides results in increased phosphorylation of eIF2α; however, it is tempting to speculate that PKR could be involved. | [
"41",
"46",
"47",
"48"
] | 191 | 227 | 0 | false | It is unclear from our data how treatment with hepatotoxic LNA oligonucleotides results in increased phosphorylation of eIF2α; however, it is tempting to speculate that PKR could be involved. | [] | It is unclear from our data how treatment with hepatotoxic LNA oligonucleotides results in increased phosphorylation of eIF2α; however, it is tempting to speculate that PKR could be involved. | true | true | true | true | true | 40 |
5 | DISCUSSION | 1 | 41 | [
"b41",
"b46",
"b47",
"b48"
] | 17,182,632 | NA|NA|NA|NA|NA|pmid-16717090|pmid-11555640|pmid-11032824|pmid-8995434 | PKR is activated by binding of dsRNA to distinct dsRNA binding domains which serve as allosteric inhibitors of the kinase domain (47,48). | [
"41",
"46",
"47",
"48"
] | 137 | 228 | 0 | false | PKR is activated by binding of dsRNA to distinct dsRNA binding domains which serve as allosteric inhibitors of the kinase domain. | [
"47,48"
] | PKR is activated by binding of dsRNA to distinct dsRNA binding domains which serve as allosteric inhibitors of the kinase domain. | true | true | true | true | true | 40 |
5 | DISCUSSION | 1 | 41 | [
"b41",
"b46",
"b47",
"b48"
] | 17,182,632 | NA|NA|NA|NA|NA|pmid-16717090|pmid-11555640|pmid-11032824|pmid-8995434 | It remains to be determined if LNA oligonucleotides interact with PKR, and more extensive mechanistic work is required to confirm both p-eIF2α mediation of an acute apoptotic response in hepatocytes, and elucidate the precise biochemical mechanism responsible for the observed hepatotoxicity. | [
"41",
"46",
"47",
"48"
] | 292 | 229 | 0 | false | It remains to be determined if LNA oligonucleotides interact with PKR, and more extensive mechanistic work is required to confirm both p-eIF2α mediation of an acute apoptotic response in hepatocytes, and elucidate the precise biochemical mechanism responsible for the observed hepatotoxicity. | [] | It remains to be determined if LNA oligonucleotides interact with PKR, and more extensive mechanistic work is required to confirm both p-eIF2α mediation of an acute apoptotic response in hepatocytes, and elucidate the precise biochemical mechanism responsible for the observed hepatotoxicity. | true | true | true | true | true | 40 |
6 | DISCUSSION | 1 | 27 | [
"b27",
"b49"
] | 17,182,632 | NA|pmid-16978088 | In conclusion, we have shown that optimization of size and gap configuration employing LNA containing ASOs can improve potency in mouse liver. | [
"27",
"49"
] | 142 | 230 | 0 | false | In conclusion, we have shown that optimization of size and gap configuration employing LNA containing ASOs can improve potency in mouse liver. | [] | In conclusion, we have shown that optimization of size and gap configuration employing LNA containing ASOs can improve potency in mouse liver. | true | true | true | true | true | 41 |
6 | DISCUSSION | 1 | 27 | [
"b27",
"b49"
] | 17,182,632 | NA|pmid-16978088 | However, this potency increase is strongly correlated with the onset of a severe hepatotoxicity not seen with the corresponding MOE ASOs, and therapeutic index is not improved. | [
"27",
"49"
] | 176 | 231 | 0 | false | However, this potency increase is strongly correlated with the onset of a severe hepatotoxicity not seen with the corresponding MOE ASOs, and therapeutic index is not improved. | [] | However, this potency increase is strongly correlated with the onset of a severe hepatotoxicity not seen with the corresponding MOE ASOs, and therapeutic index is not improved. | true | true | true | true | true | 41 |
6 | DISCUSSION | 1 | 27 | [
"b27",
"b49"
] | 17,182,632 | NA|pmid-16978088 | These results suggest that while LNA ASOs have the potential to improve potency of antisense therapeutics, they impose a significant risk of hepatotoxicity. | [
"27",
"49"
] | 156 | 232 | 0 | false | These results suggest that while LNA ASOs have the potential to improve potency of antisense therapeutics, they impose a significant risk of hepatotoxicity. | [] | These results suggest that while LNA ASOs have the potential to improve potency of antisense therapeutics, they impose a significant risk of hepatotoxicity. | true | true | true | true | true | 41 |
6 | DISCUSSION | 1 | 27 | [
"b27",
"b49"
] | 17,182,632 | NA|pmid-16978088 | The toxicities observed herein also pose challenges for interpreting target validation and pharmacology experiments using LNA ASOs in rodent models. | [
"27",
"49"
] | 148 | 233 | 0 | false | The toxicities observed herein also pose challenges for interpreting target validation and pharmacology experiments using LNA ASOs in rodent models. | [] | The toxicities observed herein also pose challenges for interpreting target validation and pharmacology experiments using LNA ASOs in rodent models. | true | true | true | true | true | 41 |
6 | DISCUSSION | 1 | 27 | [
"b27",
"b49"
] | 17,182,632 | NA|pmid-16978088 | It is possible more extensive screening efforts may identify less toxic LNA sequences, or that other ASO designs utilizing LNA may not elicit hepatotoxicity. | [
"27",
"49"
] | 157 | 234 | 0 | false | It is possible more extensive screening efforts may identify less toxic LNA sequences, or that other ASO designs utilizing LNA may not elicit hepatotoxicity. | [] | It is possible more extensive screening efforts may identify less toxic LNA sequences, or that other ASO designs utilizing LNA may not elicit hepatotoxicity. | true | true | true | true | true | 41 |
6 | DISCUSSION | 1 | 27 | [
"b27",
"b49"
] | 17,182,632 | NA|pmid-16978088 | Additionally, bicyclic nucleosides similar to LNA such as amino-LNA, thio-LNA (27) and ENA (which contains one extra methylene unit in the bicyclic bridge) (49) have been reported to show antisense effects similar to LNA and MOE ASOs. | [
"27",
"49"
] | 234 | 235 | 1 | false | Additionally, bicyclic nucleosides similar to LNA such as amino-LNA, thio-LNA and ENA (which contains one extra methylene unit in the bicyclic bridge) have been reported to show antisense effects similar to LNA and MOE ASOs. | [
"27",
"49"
] | Additionally, bicyclic nucleosides similar to LNA such as amino-LNA, thio-LNA and ENA (which contains one extra methylene unit in the bicyclic bridge) have been reported to show antisense effects similar to LNA and MOE ASOs. | true | true | true | true | true | 41 |
6 | DISCUSSION | 1 | 27 | [
"b27",
"b49"
] | 17,182,632 | NA|pmid-16978088 | Although optimized designs of one or more of these modifications may ultimately improve potency while maintaining the safety profile of MOE ASOs, no detailed characterization of their toxicological properties has yet been reported. | [
"27",
"49"
] | 231 | 236 | 0 | false | Although optimized designs of one or more of these modifications may ultimately improve potency while maintaining the safety profile of MOE ASOs, no detailed characterization of their toxicological properties has yet been reported. | [] | Although optimized designs of one or more of these modifications may ultimately improve potency while maintaining the safety profile of MOE ASOs, no detailed characterization of their toxicological properties has yet been reported. | true | true | true | true | true | 41 |
6 | DISCUSSION | 1 | 27 | [
"b27",
"b49"
] | 17,182,632 | NA|pmid-16978088 | It is clear that additional structure–activity and structure–toxicity relationship studies will be required to more fully assess the therapeutic potential of LNA and other bicyclic nucleoside modified oligonucleotides. | [
"27",
"49"
] | 218 | 237 | 0 | false | It is clear that additional structure–activity and structure–toxicity relationship studies will be required to more fully assess the therapeutic potential of LNA and other bicyclic nucleoside modified oligonucleotides. | [] | It is clear that additional structure–activity and structure–toxicity relationship studies will be required to more fully assess the therapeutic potential of LNA and other bicyclic nucleoside modified oligonucleotides. | true | true | true | true | true | 41 |
6 | DISCUSSION | 1 | 27 | [
"b27",
"b49"
] | 17,182,632 | NA|pmid-16978088 | Ultimately, the value of LNA oligonucleotide drugs will be determined in human clinical trials, where they are currently being developed for the treatment of cancer. | [
"27",
"49"
] | 165 | 238 | 0 | false | Ultimately, the value of LNA oligonucleotide drugs will be determined in human clinical trials, where they are currently being developed for the treatment of cancer. | [] | Ultimately, the value of LNA oligonucleotide drugs will be determined in human clinical trials, where they are currently being developed for the treatment of cancer. | true | true | true | true | true | 41 |
6 | DISCUSSION | 1 | 27 | [
"b27",
"b49"
] | 17,182,632 | NA|pmid-16978088 | Our results are based only on studies in rodents; however, caution should be exercised in the clinical development of LNA modified oligonucleotides, especially for chronic, non-life threatening indications. | [
"27",
"49"
] | 206 | 239 | 0 | false | Our results are based only on studies in rodents; however, caution should be exercised in the clinical development of LNA modified oligonucleotides, especially for chronic, non-life threatening indications. | [] | Our results are based only on studies in rodents; however, caution should be exercised in the clinical development of LNA modified oligonucleotides, especially for chronic, non-life threatening indications. | true | true | true | true | true | 41 |
0 | INTRODUCTION | 1 | 1–4 | [
"B1 B2 B3 B4",
"B1",
"B5"
] | 17,567,608 | pmid-15568977|pmid-10357855|pmid-11516927|pmid-10754547|pmid-15568977|pmid-12142524 | Homologous recombination (HR) is a template-dependent, high-fidelity DNA damage repair and tolerance pathway that negotiates complex DNA damage, such as double-stranded DNA breaks (DSBs), gaps, and interstrand crosslinks, as well as stalled or collapsed replication forks (1–4). | [
"1–4",
"1",
"5"
] | 278 | 240 | 1 | false | Homologous recombination (HR) is a template-dependent, high-fidelity DNA damage repair and tolerance pathway that negotiates complex DNA damage, such as double-stranded DNA breaks (DSBs), gaps, and interstrand crosslinks, as well as stalled or collapsed replication forks. | [
"1–4"
] | Homologous recombination (HR) is a template-dependent, high-fidelity DNA damage repair and tolerance pathway that negotiates complex DNA damage, such as double-stranded DNA breaks (DSBs), gaps, and interstrand crosslinks, as well as stalled or collapsed replication forks. | true | true | true | true | true | 42 |
0 | INTRODUCTION | 1 | 1–4 | [
"B1 B2 B3 B4",
"B1",
"B5"
] | 17,567,608 | pmid-15568977|pmid-10357855|pmid-11516927|pmid-10754547|pmid-15568977|pmid-12142524 | Defects in HR lead to sensitivity to genotoxic agents and genomic instability (1,5). | [
"1–4",
"1",
"5"
] | 84 | 241 | 0 | false | Defects in HR lead to sensitivity to genotoxic agents and genomic instability. | [
"1,5"
] | Defects in HR lead to sensitivity to genotoxic agents and genomic instability. | true | true | true | true | true | 42 |
1 | INTRODUCTION | 1 | 10 | [
"B10",
"B2"
] | 17,567,608 | pmid-8066464|pmid-10357855|pmid-6329717|pmid-8910403|pmid-11030336|pmid-11030336|pmid-12192033|pmid-17302439 | The process of HR can be conceptually divided into three stages. | [
"10",
"2"
] | 64 | 242 | 0 | false | The process of HR can be conceptually divided into three stages. | [] | The process of HR can be conceptually divided into three stages. | true | true | true | true | true | 43 |
1 | INTRODUCTION | 1 | 10 | [
"B10",
"B2"
] | 17,567,608 | pmid-8066464|pmid-10357855|pmid-6329717|pmid-8910403|pmid-11030336|pmid-11030336|pmid-12192033|pmid-17302439 | In presynapsis, the lesion is processed to a single-stranded DNA (ssDNA) intermediate. | [
"10",
"2"
] | 86 | 243 | 0 | false | In presynapsis, the lesion is processed to a single-stranded DNA (ssDNA) intermediate. | [] | In presynapsis, the lesion is processed to a single-stranded DNA (ssDNA) intermediate. | true | true | true | true | true | 43 |
1 | INTRODUCTION | 1 | 10 | [
"B10",
"B2"
] | 17,567,608 | pmid-8066464|pmid-10357855|pmid-6329717|pmid-8910403|pmid-11030336|pmid-11030336|pmid-12192033|pmid-17302439 | In vivo, ssDNA is likely bound by the ssDNA-binding protein RPA, requiring mediator proteins, such as Rad52 and the Rad55-Rad57 heterodimer, to allow formation of the presynaptic filament of Rad51-ATP-ssDNA (6–9). | [
"10",
"2"
] | 213 | 244 | 0 | false | In vivo, ssDNA is likely bound by the ssDNA-binding protein RPA, requiring mediator proteins, such as Rad52 and the Rad55-Rad57 heterodimer, to allow formation of the presynaptic filament of Rad51-ATP-ssDNA (6–9). | [] | In vivo, ssDNA is likely bound by the ssDNA-binding protein RPA, requiring mediator proteins, such as Rad52 and the Rad55-Rad57 heterodimer, to allow formation of the presynaptic filament of Rad51-ATP-ssDNA (6–9). | true | true | true | true | true | 43 |
1 | INTRODUCTION | 1 | 10 | [
"B10",
"B2"
] | 17,567,608 | pmid-8066464|pmid-10357855|pmid-6329717|pmid-8910403|pmid-11030336|pmid-11030336|pmid-12192033|pmid-17302439 | During synapsis, the presynaptic filament mediates homology search and DNA strand invasion to form a joint molecule or D–loop (10). | [
"10",
"2"
] | 131 | 245 | 1 | false | During synapsis, the presynaptic filament mediates homology search and DNA strand invasion to form a joint molecule or D–loop. | [
"10"
] | During synapsis, the presynaptic filament mediates homology search and DNA strand invasion to form a joint molecule or D–loop. | true | true | true | true | true | 43 |
1 | INTRODUCTION | 1 | 10 | [
"B10",
"B2"
] | 17,567,608 | pmid-8066464|pmid-10357855|pmid-6329717|pmid-8910403|pmid-11030336|pmid-11030336|pmid-12192033|pmid-17302439 | In postsynapsis, Rad51 is assumed to dissociate from the product heteroduplex DNA to allow DNA synthesis from the invading 3′ end. | [
"10",
"2"
] | 130 | 246 | 0 | false | In postsynapsis, Rad51 is assumed to dissociate from the product heteroduplex DNA to allow DNA synthesis from the invading 3′ end. | [] | In postsynapsis, Rad51 is assumed to dissociate from the product heteroduplex DNA to allow DNA synthesis from the invading 3′ end. | true | true | true | true | true | 43 |
1 | INTRODUCTION | 1 | 2 | [
"B10",
"B2"
] | 17,567,608 | pmid-8066464|pmid-10357855|pmid-6329717|pmid-8910403|pmid-11030336|pmid-11030336|pmid-12192033|pmid-17302439 | After DNA synthesis, different sub-pathways (Synthesis-Dependent Strand Annealing, DSB Repair) generate contiguous chromosomes (2). | [
"10",
"2"
] | 131 | 247 | 1 | false | After DNA synthesis, different sub-pathways (Synthesis-Dependent Strand Annealing, DSB Repair) generate contiguous chromosomes. | [
"2"
] | After DNA synthesis, different sub-pathways (Synthesis-Dependent Strand Annealing, DSB Repair) generate contiguous chromosomes. | true | true | true | true | true | 43 |
2 | INTRODUCTION | 1 | 1 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | Rad51 and Rad54 are two key proteins in HR (1). | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 47 | 248 | 1 | false | Rad51 and Rad54 are two key proteins in HR. | [
"1"
] | Rad51 and Rad54 are two key proteins in HR. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 1 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | Like RecA, Rad51 forms a helical filament on DNA in the presence of ATP and catalyzes homology search and DNA strand invasion (10–13). | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 134 | 249 | 0 | false | Like RecA, Rad51 forms a helical filament on DNA in the presence of ATP and catalyzes homology search and DNA strand invasion. | [
"10–13"
] | Like RecA, Rad51 forms a helical filament on DNA in the presence of ATP and catalyzes homology search and DNA strand invasion. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 1 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | This reaction produces heteroduplex DNA, a central recombination intermediate. | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 78 | 250 | 0 | false | This reaction produces heteroduplex DNA, a central recombination intermediate. | [] | This reaction produces heteroduplex DNA, a central recombination intermediate. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 1 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | DNA-binding and DNA-strand exchange activity by budding yeast Rad51 in vitro requires ATP-binding but not ATP hydrolysis as revealed by the analysis of mutants in the invariant lysine residue within the Walker A box (K191 in budding yeast), as well as by using slow or non-hydrolyzable ATP analogs (10,14–19). | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 309 | 251 | 0 | false | DNA-binding and DNA-strand exchange activity by budding yeast Rad51 in vitro requires ATP-binding but not ATP hydrolysis as revealed by the analysis of mutants in the invariant lysine residue within the Walker A box, as well as by using slow or non-hydrolyzable ATP analogs. | [
"K191 in budding yeast",
"10,14–19"
] | DNA-binding and DNA-strand exchange activity by budding yeast Rad51 in vitro requires ATP-binding but not ATP hydrolysis as revealed by the analysis of mutants in the invariant lysine residue within the Walker A box, as well as by using slow or non-hydrolyzable ATP analogs. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 20 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | However, in vivo ATP hydrolysis appears to be required for protein function (20). | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 81 | 252 | 1 | false | However, in vivo ATP hydrolysis appears to be required for protein function. | [
"20"
] | However, in vivo ATP hydrolysis appears to be required for protein function. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 14 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | Saccharomyces cerevisiae Rad51-K191R encodes a protein that can presumably bind ATP, although this was never directly demonstrated, but not hydrolyze ATP (14). | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 159 | 253 | 1 | false | Saccharomyces cerevisiae Rad51-K191R encodes a protein that can presumably bind ATP, although this was never directly demonstrated, but not hydrolyze ATP. | [
"14"
] | Saccharomyces cerevisiae Rad51-K191R encodes a protein that can presumably bind ATP, although this was never directly demonstrated, but not hydrolyze ATP. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 20 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | The mutant protein when expressed at native levels in haploid cells conferred severe sensitivity to IR and a DSB-repair defect (20). | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 132 | 254 | 1 | false | The mutant protein when expressed at native levels in haploid cells conferred severe sensitivity to IR and a DSB-repair defect. | [
"20"
] | The mutant protein when expressed at native levels in haploid cells conferred severe sensitivity to IR and a DSB-repair defect. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 1 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | Similarly, the equivalent RecA mutant (RecA-K72R) cannot complement the UV sensitivity of a RecA-deficient strain (21,22). | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 122 | 255 | 0 | false | Similarly, the equivalent RecA mutant (RecA-K72R) cannot complement the UV sensitivity of a RecA-deficient strain. | [
"21,22"
] | Similarly, the equivalent RecA mutant (RecA-K72R) cannot complement the UV sensitivity of a RecA-deficient strain. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 1 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | Other ATPase defective RecA mutants show less severe defects in vivo (23,24). | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 77 | 256 | 0 | false | Other ATPase defective RecA mutants show less severe defects in vivo. | [
"23,24"
] | Other ATPase defective RecA mutants show less severe defects in vivo. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 1 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | When expressed at high levels, budding yeast Rad51-K191R complements the MMS- and IR-sensitivity of a Rad51-deficient strain to near completion (14,20). | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 152 | 257 | 0 | false | When expressed at high levels, budding yeast Rad51-K191R complements the MMS- and IR-sensitivity of a Rad51-deficient strain to near completion. | [
"14,20"
] | When expressed at high levels, budding yeast Rad51-K191R complements the MMS- and IR-sensitivity of a Rad51-deficient strain to near completion. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 1 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | The importance of ATP hydrolysis for the in vivo function of RecA-like proteins is underlined by the dominant-negative effect exerted by the equivalent human Rad51-K133R mutant protein when expressed in mouse, chicken or human cells (25–28). | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 241 | 258 | 0 | false | The importance of ATP hydrolysis for the in vivo function of RecA-like proteins is underlined by the dominant-negative effect exerted by the equivalent human Rad51-K133R mutant protein when expressed in mouse, chicken or human cells (25–28). | [] | The importance of ATP hydrolysis for the in vivo function of RecA-like proteins is underlined by the dominant-negative effect exerted by the equivalent human Rad51-K133R mutant protein when expressed in mouse, chicken or human cells (25–28). | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 1 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | The in vitro and in vivo results regarding the requirement of ATP hydrolysis for Rad51 (RecA) function present an apparent contradiction. | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 137 | 259 | 0 | false | The in vitro and in vivo results regarding the requirement of ATP hydrolysis for Rad51 (RecA) function present an apparent contradiction. | [] | The in vitro and in vivo results regarding the requirement of ATP hydrolysis for Rad51 (RecA) function present an apparent contradiction. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 1 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | However, in vitro DNA strand invasion assays typically sidestep the requirement for product release by Rad51 (or RecA), which is achieved by SDS/proteinase K treatment. | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 168 | 260 | 0 | false | However, in vitro DNA strand invasion assays typically sidestep the requirement for product release by Rad51 (or RecA), which is achieved by SDS/proteinase K treatment. | [] | However, in vitro DNA strand invasion assays typically sidestep the requirement for product release by Rad51 (or RecA), which is achieved by SDS/proteinase K treatment. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 1 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | Indeed, biochemical and electron microscopic analysis of the human Rad51 protein showed that Rad51-DNA complexes are stabilized under conditions that inhibit ATP hydrolysis (15,16), suggesting a need of ATP hydrolysis for Rad51 turnover from dsDNA. | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 248 | 261 | 0 | false | Indeed, biochemical and electron microscopic analysis of the human Rad51 protein showed that Rad51-DNA complexes are stabilized under conditions that inhibit ATP hydrolysis, suggesting a need of ATP hydrolysis for Rad51 turnover from dsDNA. | [
"15,16"
] | Indeed, biochemical and electron microscopic analysis of the human Rad51 protein showed that Rad51-DNA complexes are stabilized under conditions that inhibit ATP hydrolysis, suggesting a need of ATP hydrolysis for Rad51 turnover from dsDNA. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 19 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | Also experiments with RecA protein have demonstrated the need for ATP hydrolysis to release the heteroduplex product (19). | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 122 | 262 | 1 | false | Also experiments with RecA protein have demonstrated the need for ATP hydrolysis to release the heteroduplex product. | [
"19"
] | Also experiments with RecA protein have demonstrated the need for ATP hydrolysis to release the heteroduplex product. | true | true | true | true | true | 44 |
2 | INTRODUCTION | 1 | 1 | [
"B1",
"B20",
"B14",
"B20",
"B21",
"B22",
"B23",
"B24",
"B14",
"B20",
"B15",
"B16",
"B19"
] | 17,567,608 | pmid-15568977|pmid-12192033|pmid-8910403|pmid-12192033|pmid-8133517|pmid-8371266|pmid-9973562|pmid-9973561|pmid-8910403|pmid-12192033|pmid-16388992|NA|pmid-2147722|pmid-17030607|pmid-12359723|pmid-16979659|pmid-16388992|NA | These experiments suggest that ATP hydrolysis by Rad51 is needed to enhance filament dynamics. | [
"1",
"20",
"14",
"20",
"21",
"22",
"23",
"24",
"14",
"20",
"15",
"16",
"19"
] | 94 | 263 | 0 | false | These experiments suggest that ATP hydrolysis by Rad51 is needed to enhance filament dynamics. | [] | These experiments suggest that ATP hydrolysis by Rad51 is needed to enhance filament dynamics. | true | true | true | true | true | 44 |
3 | INTRODUCTION | 1 | 31 | [
"B29",
"B30",
"B31",
"B1",
"B32",
"B29",
"B30",
"B50",
"B51",
"B52",
"B53"
] | 17,567,608 | pmid-12826279|pmid-16935872|pmid-16818238|pmid-15568977|pmid-12560498|pmid-12826279|pmid-16935872|pmid-11459988|pmid-16862129|pmid-8631697|pmid-12087154|pmid-12192033|pmid-17030607|pmid-12192033|pmid-17030607|pmid-12748644|pmid-12748645|pmid-12192033|pmid-16980587 | Rad54 protein is a member of the Swi2/Snf2 family of dsDNA-dependent ATPases (29,30) and processively translocates along the dsDNA lattice at up to 300 bp/sec (31). | [
"29",
"30",
"31",
"1",
"32",
"29",
"30",
"50",
"51",
"52",
"53"
] | 164 | 264 | 1 | false | Rad54 protein is a member of the Swi2/Snf2 family of dsDNA-dependent ATPases and processively translocates along the dsDNA lattice at up to 300 bp/sec. | [
"29,30",
"31"
] | Rad54 protein is a member of the Swi2/Snf2 family of dsDNA-dependent ATPases and processively translocates along the dsDNA lattice at up to 300 bp/sec. | true | true | true | true | true | 45 |
3 | INTRODUCTION | 1 | 29 | [
"B29",
"B30",
"B31",
"B1",
"B32",
"B29",
"B30",
"B50",
"B51",
"B52",
"B53"
] | 17,567,608 | pmid-12826279|pmid-16935872|pmid-16818238|pmid-15568977|pmid-12560498|pmid-12826279|pmid-16935872|pmid-11459988|pmid-16862129|pmid-8631697|pmid-12087154|pmid-12192033|pmid-17030607|pmid-12192033|pmid-17030607|pmid-12748644|pmid-12748645|pmid-12192033|pmid-16980587 | Deletion of the RAD54 gene in budding yeast confers as strong a mitotic recombination defect or IR sensitivity as a deficiency in the RAD51 gene (1,32). | [
"29",
"30",
"31",
"1",
"32",
"29",
"30",
"50",
"51",
"52",
"53"
] | 152 | 265 | 0 | false | Deletion of the RAD54 gene in budding yeast confers as strong a mitotic recombination defect or IR sensitivity as a deficiency in the RAD51 gene. | [
"1,32"
] | Deletion of the RAD54 gene in budding yeast confers as strong a mitotic recombination defect or IR sensitivity as a deficiency in the RAD51 gene. | true | true | true | true | true | 45 |
3 | INTRODUCTION | 1 | 29 | [
"B29",
"B30",
"B31",
"B1",
"B32",
"B29",
"B30",
"B50",
"B51",
"B52",
"B53"
] | 17,567,608 | pmid-12826279|pmid-16935872|pmid-16818238|pmid-15568977|pmid-12560498|pmid-12826279|pmid-16935872|pmid-11459988|pmid-16862129|pmid-8631697|pmid-12087154|pmid-12192033|pmid-17030607|pmid-12192033|pmid-17030607|pmid-12748644|pmid-12748645|pmid-12192033|pmid-16980587 | In vivo function of Rad54 protein is largely compromised in the rad54-K341R mutant, which encodes a mutant Rad54 protein that is defective in ATP hydrolysis (33–36). | [
"29",
"30",
"31",
"1",
"32",
"29",
"30",
"50",
"51",
"52",
"53"
] | 165 | 266 | 0 | false | In vivo function of Rad54 protein is largely compromised in the rad54-K341R mutant, which encodes a mutant Rad54 protein that is defective in ATP hydrolysis (33–36). | [] | In vivo function of Rad54 protein is largely compromised in the rad54-K341R mutant, which encodes a mutant Rad54 protein that is defective in ATP hydrolysis (33–36). | true | true | true | true | true | 45 |
3 | INTRODUCTION | 1 | 29 | [
"B29",
"B30",
"B31",
"B1",
"B32",
"B29",
"B30",
"B50",
"B51",
"B52",
"B53"
] | 17,567,608 | pmid-12826279|pmid-16935872|pmid-16818238|pmid-15568977|pmid-12560498|pmid-12826279|pmid-16935872|pmid-11459988|pmid-16862129|pmid-8631697|pmid-12087154|pmid-12192033|pmid-17030607|pmid-12192033|pmid-17030607|pmid-12748644|pmid-12748645|pmid-12192033|pmid-16980587 | Rad51 and Rad54 act in a single molecular pathway and physically interact (37–39). | [
"29",
"30",
"31",
"1",
"32",
"29",
"30",
"50",
"51",
"52",
"53"
] | 82 | 267 | 0 | false | Rad51 and Rad54 act in a single molecular pathway and physically interact (37–39). | [] | Rad51 and Rad54 act in a single molecular pathway and physically interact. | true | true | true | true | true | 45 |
3 | INTRODUCTION | 1 | 29 | [
"B29",
"B30",
"B31",
"B1",
"B32",
"B29",
"B30",
"B50",
"B51",
"B52",
"B53"
] | 17,567,608 | pmid-12826279|pmid-16935872|pmid-16818238|pmid-15568977|pmid-12560498|pmid-12826279|pmid-16935872|pmid-11459988|pmid-16862129|pmid-8631697|pmid-12087154|pmid-12192033|pmid-17030607|pmid-12192033|pmid-17030607|pmid-12748644|pmid-12748645|pmid-12192033|pmid-16980587 | Rad54 was found to stabilize Rad51-ssDNA filaments in the presynaptic phase of recombination in an ATPase-independent fashion (40–42). | [
"29",
"30",
"31",
"1",
"32",
"29",
"30",
"50",
"51",
"52",
"53"
] | 134 | 268 | 0 | false | Rad54 was found to stabilize Rad51-ssDNA filaments in the presynaptic phase of recombination in an ATPase-independent fashion (40–42). | [] | Rad54 was found to stabilize Rad51-ssDNA filaments in the presynaptic phase of recombination in an ATPase-independent fashion. | true | true | true | true | true | 45 |
3 | INTRODUCTION | 1 | 29 | [
"B29",
"B30",
"B31",
"B1",
"B32",
"B29",
"B30",
"B50",
"B51",
"B52",
"B53"
] | 17,567,608 | pmid-12826279|pmid-16935872|pmid-16818238|pmid-15568977|pmid-12560498|pmid-12826279|pmid-16935872|pmid-11459988|pmid-16862129|pmid-8631697|pmid-12087154|pmid-12192033|pmid-17030607|pmid-12192033|pmid-17030607|pmid-12748644|pmid-12748645|pmid-12192033|pmid-16980587 | Rad54 also stimulates DNA strand exchange at the synaptic stage (35,43–46). | [
"29",
"30",
"31",
"1",
"32",
"29",
"30",
"50",
"51",
"52",
"53"
] | 75 | 269 | 0 | false | Rad54 also stimulates DNA strand exchange at the synaptic stage (35,43–46). | [] | Rad54 also stimulates DNA strand exchange at the synaptic stage (35,43–46). | true | true | true | true | true | 45 |
3 | INTRODUCTION | 1 | 29 | [
"B29",
"B30",
"B31",
"B1",
"B32",
"B29",
"B30",
"B50",
"B51",
"B52",
"B53"
] | 17,567,608 | pmid-12826279|pmid-16935872|pmid-16818238|pmid-15568977|pmid-12560498|pmid-12826279|pmid-16935872|pmid-11459988|pmid-16862129|pmid-8631697|pmid-12087154|pmid-12192033|pmid-17030607|pmid-12192033|pmid-17030607|pmid-12748644|pmid-12748645|pmid-12192033|pmid-16980587 | The mechanism of this stimulation is not fully understood but requires the motor function of Rad54 and depends on its ATPase activity. | [
"29",
"30",
"31",
"1",
"32",
"29",
"30",
"50",
"51",
"52",
"53"
] | 134 | 270 | 0 | false | The mechanism of this stimulation is not fully understood but requires the motor function of Rad54 and depends on its ATPase activity. | [] | The mechanism of this stimulation is not fully understood but requires the motor function of Rad54 and depends on its ATPase activity. | true | true | true | true | true | 45 |
3 | INTRODUCTION | 1 | 29 | [
"B29",
"B30",
"B31",
"B1",
"B32",
"B29",
"B30",
"B50",
"B51",
"B52",
"B53"
] | 17,567,608 | pmid-12826279|pmid-16935872|pmid-16818238|pmid-15568977|pmid-12560498|pmid-12826279|pmid-16935872|pmid-11459988|pmid-16862129|pmid-8631697|pmid-12087154|pmid-12192033|pmid-17030607|pmid-12192033|pmid-17030607|pmid-12748644|pmid-12748645|pmid-12192033|pmid-16980587 | Possible mechanisms include the sliding of the target dsDNA during homology search, opening the target dsDNA by translocating on duplex DNA, or removing Rad51 from dsDNA that inhibit Rad51-mediated DNA strand exchange (29,30). | [
"29",
"30",
"31",
"1",
"32",
"29",
"30",
"50",
"51",
"52",
"53"
] | 226 | 271 | 0 | false | Possible mechanisms include the sliding of the target dsDNA during homology search, opening the target dsDNA by translocating on duplex DNA, or removing Rad51 from dsDNA that inhibit Rad51-mediated DNA strand exchange. | [
"29,30"
] | Possible mechanisms include the sliding of the target dsDNA during homology search, opening the target dsDNA by translocating on duplex DNA, or removing Rad51 from dsDNA that inhibit Rad51-mediated DNA strand exchange. | true | true | true | true | true | 45 |
3 | INTRODUCTION | 1 | 29 | [
"B29",
"B30",
"B31",
"B1",
"B32",
"B29",
"B30",
"B50",
"B51",
"B52",
"B53"
] | 17,567,608 | pmid-12826279|pmid-16935872|pmid-16818238|pmid-15568977|pmid-12560498|pmid-12826279|pmid-16935872|pmid-11459988|pmid-16862129|pmid-8631697|pmid-12087154|pmid-12192033|pmid-17030607|pmid-12192033|pmid-17030607|pmid-12748644|pmid-12748645|pmid-12192033|pmid-16980587 | Moreover, Rad54 was demonstrated to be able to remodel nucleosomes in vitro, although no effect of Rad54 on nucleosome positioning during DSB repair has been identified in budding yeast (42,47–49). | [
"29",
"30",
"31",
"1",
"32",
"29",
"30",
"50",
"51",
"52",
"53"
] | 197 | 272 | 0 | false | Moreover, Rad54 was demonstrated to be able to remodel nucleosomes in vitro, although no effect of Rad54 on nucleosome positioning during DSB repair has been identified in budding yeast (42,47–49). | [] | Moreover, Rad54 was demonstrated to be able to remodel nucleosomes in vitro, although no effect of Rad54 on nucleosome positioning during DSB repair has been identified in budding yeast. | true | true | true | true | true | 45 |
3 | INTRODUCTION | 1 | 52 | [
"B29",
"B30",
"B31",
"B1",
"B32",
"B29",
"B30",
"B50",
"B51",
"B52",
"B53"
] | 17,567,608 | pmid-12826279|pmid-16935872|pmid-16818238|pmid-15568977|pmid-12560498|pmid-12826279|pmid-16935872|pmid-11459988|pmid-16862129|pmid-8631697|pmid-12087154|pmid-12192033|pmid-17030607|pmid-12192033|pmid-17030607|pmid-12748644|pmid-12748645|pmid-12192033|pmid-16980587 | During postsynapsis, Rad54 was shown to enhance branch migration during DNA strand exchange (50,51), but it is unclear whether Rad54 acts as a junction-specific motor protein like RuvB in bacteria (52). | [
"29",
"30",
"31",
"1",
"32",
"29",
"30",
"50",
"51",
"52",
"53"
] | 202 | 273 | 1 | false | During postsynapsis, Rad54 was shown to enhance branch migration during DNA strand exchange, but it is unclear whether Rad54 acts as a junction-specific motor protein like RuvB in bacteria. | [
"50,51",
"52"
] | During postsynapsis, Rad54 was shown to enhance branch migration during DNA strand exchange, but it is unclear whether Rad54 acts as a junction-specific motor protein like RuvB in bacteria. | true | true | true | true | true | 45 |
3 | INTRODUCTION | 1 | 53 | [
"B29",
"B30",
"B31",
"B1",
"B32",
"B29",
"B30",
"B50",
"B51",
"B52",
"B53"
] | 17,567,608 | pmid-12826279|pmid-16935872|pmid-16818238|pmid-15568977|pmid-12560498|pmid-12826279|pmid-16935872|pmid-11459988|pmid-16862129|pmid-8631697|pmid-12087154|pmid-12192033|pmid-17030607|pmid-12192033|pmid-17030607|pmid-12748644|pmid-12748645|pmid-12192033|pmid-16980587 | Overexpression of Rad54 leads to a decrease in conversion tract length (53) not increase as predicted, if Rad54 were to drive branch migration. | [
"29",
"30",
"31",
"1",
"32",
"29",
"30",
"50",
"51",
"52",
"53"
] | 143 | 274 | 1 | false | Overexpression of Rad54 leads to a decrease in conversion tract length not increase as predicted, if Rad54 were to drive branch migration. | [
"53"
] | Overexpression of Rad54 leads to a decrease in conversion tract length not increase as predicted, if Rad54 were to drive branch migration. | true | true | true | true | true | 45 |
4 | INTRODUCTION | 1 | 59 | [
"B59",
"B60",
"B61",
"B41",
"B62"
] | 17,567,608 | pmid-12887907|pmid-12887906|pmid-12359723|pmid-12453424|pmid-16785421|pmid-12359723|pmid-16818238|pmid-16916635|pmid-16785421 | Genetic analysis suggests that Rad54 acts at a step after Rad51 protein, consistent with cytological data showing that RAD54 is not required for Rad51 focus formation (54–58). | [
"59",
"60",
"61",
"41",
"62"
] | 175 | 275 | 0 | false | Genetic analysis suggests that Rad54 acts at a step after Rad51 protein, consistent with cytological data showing that RAD54 is not required for Rad51 focus formation (54–58). | [] | Genetic analysis suggests that Rad54 acts at a step after Rad51 protein, consistent with cytological data showing that RAD54 is not required for Rad51 focus formation. | true | true | true | true | true | 46 |
4 | INTRODUCTION | 1 | 59 | [
"B59",
"B60",
"B61",
"B41",
"B62"
] | 17,567,608 | pmid-12887907|pmid-12887906|pmid-12359723|pmid-12453424|pmid-16785421|pmid-12359723|pmid-16818238|pmid-16916635|pmid-16785421 | Together with data from chromatin immunoprecipitation experiments (59,60), these results suggest that the critical function of Rad54 is either during synapsis or postsynapsis but the results are not able to distinguish between both possibilities. | [
"59",
"60",
"61",
"41",
"62"
] | 246 | 276 | 0 | false | Together with data from chromatin immunoprecipitation experiments, these results suggest that the critical function of Rad54 is either during synapsis or postsynapsis but the results are not able to distinguish between both possibilities. | [
"59,60"
] | Together with data from chromatin immunoprecipitation experiments, these results suggest that the critical function of Rad54 is either during synapsis or postsynapsis but the results are not able to distinguish between both possibilities. | true | true | true | true | true | 46 |
4 | INTRODUCTION | 1 | 61 | [
"B59",
"B60",
"B61",
"B41",
"B62"
] | 17,567,608 | pmid-12887907|pmid-12887906|pmid-12359723|pmid-12453424|pmid-16785421|pmid-12359723|pmid-16818238|pmid-16916635|pmid-16785421 | Since Rad54 is a dsDNA motor protein that interacts with Rad51, we have focused on the interaction between Rad54 and the Rad51-dsDNA filament (61). | [
"59",
"60",
"61",
"41",
"62"
] | 147 | 277 | 1 | false | Since Rad54 is a dsDNA motor protein that interacts with Rad51, we have focused on the interaction between Rad54 and the Rad51-dsDNA filament. | [
"61"
] | Since Rad54 is a dsDNA motor protein that interacts with Rad51, we have focused on the interaction between Rad54 and the Rad51-dsDNA filament. | true | true | true | true | true | 46 |
4 | INTRODUCTION | 1 | 41 | [
"B59",
"B60",
"B61",
"B41",
"B62"
] | 17,567,608 | pmid-12887907|pmid-12887906|pmid-12359723|pmid-12453424|pmid-16785421|pmid-12359723|pmid-16818238|pmid-16916635|pmid-16785421 | We discovered that Rad54 remodels the Rad51-dsDNA filament, resulting in the dissociation of Rad51 from dsDNA (41). | [
"59",
"60",
"61",
"41",
"62"
] | 115 | 278 | 1 | false | We discovered that Rad54 remodels the Rad51-dsDNA filament, resulting in the dissociation of Rad51 from dsDNA. | [
"41"
] | We discovered that Rad54 remodels the Rad51-dsDNA filament, resulting in the dissociation of Rad51 from dsDNA. | true | true | true | true | true | 46 |
4 | INTRODUCTION | 1 | 62 | [
"B59",
"B60",
"B61",
"B41",
"B62"
] | 17,567,608 | pmid-12887907|pmid-12887906|pmid-12359723|pmid-12453424|pmid-16785421|pmid-12359723|pmid-16818238|pmid-16916635|pmid-16785421 | Using electron microscopic analysis, Rad54 was found to preferentially localize to one terminus of the Rad51-dsDNA filament, consistent with Rad54 translocating along dsDNA and then docking at the end of the Rad51 filament or directly binding the filament end from solution (62). | [
"59",
"60",
"61",
"41",
"62"
] | 279 | 279 | 1 | false | Using electron microscopic analysis, Rad54 was found to preferentially localize to one terminus of the Rad51-dsDNA filament, consistent with Rad54 translocating along dsDNA and then docking at the end of the Rad51 filament or directly binding the filament end from solution. | [
"62"
] | Using electron microscopic analysis, Rad54 was found to preferentially localize to one terminus of the Rad51-dsDNA filament, consistent with Rad54 translocating along dsDNA and then docking at the end of the Rad51 filament or directly binding the filament end from solution. | true | true | true | true | true | 46 |
4 | INTRODUCTION | 1 | 59 | [
"B59",
"B60",
"B61",
"B41",
"B62"
] | 17,567,608 | pmid-12887907|pmid-12887906|pmid-12359723|pmid-12453424|pmid-16785421|pmid-12359723|pmid-16818238|pmid-16916635|pmid-16785421 | These data support a model, in which Rad54 acts as a turnover factor for the Rad51-heteroduplex DNA product complex, resulting in product release by Rad51 to allow access of the DNA synthesis machinery to the invading 3′ end. | [
"59",
"60",
"61",
"41",
"62"
] | 225 | 280 | 0 | false | These data support a model, in which Rad54 acts as a turnover factor for the Rad51-heteroduplex DNA product complex, resulting in product release by Rad51 to allow access of the DNA synthesis machinery to the invading 3′ end. | [] | These data support a model, in which Rad54 acts as a turnover factor for the Rad51-heteroduplex DNA product complex, resulting in product release by Rad51 to allow access of the DNA synthesis machinery to the invading 3′ end. | true | true | true | true | true | 46 |
4 | INTRODUCTION | 1 | 59 | [
"B59",
"B60",
"B61",
"B41",
"B62"
] | 17,567,608 | pmid-12887907|pmid-12887906|pmid-12359723|pmid-12453424|pmid-16785421|pmid-12359723|pmid-16818238|pmid-16916635|pmid-16785421 | This model also rationalizes significant differences between RecA and Rad51. | [
"59",
"60",
"61",
"41",
"62"
] | 76 | 281 | 0 | false | This model also rationalizes significant differences between RecA and Rad51. | [] | This model also rationalizes significant differences between RecA and Rad51. | true | true | true | true | true | 46 |
4 | INTRODUCTION | 1 | 59 | [
"B59",
"B60",
"B61",
"B41",
"B62"
] | 17,567,608 | pmid-12887907|pmid-12887906|pmid-12359723|pmid-12453424|pmid-16785421|pmid-12359723|pmid-16818238|pmid-16916635|pmid-16785421 | RecA exhibits ∼200-fold higher ATPase activity on dsDNA and releases from DNA after ATP hydrolysis, whereas Rad51 appears to be much less dynamic in filament assembly/disassembly (10,15,16,19). | [
"59",
"60",
"61",
"41",
"62"
] | 193 | 282 | 0 | false | RecA exhibits ∼200-fold higher ATPase activity on dsDNA and releases from DNA after ATP hydrolysis, whereas Rad51 appears to be much less dynamic in filament assembly/disassembly (10,15,16,19). | [] | RecA exhibits ∼200-fold higher ATPase activity on dsDNA and releases from DNA after ATP hydrolysis, whereas Rad51 appears to be much less dynamic in filament assembly/disassembly. | true | true | true | true | true | 46 |
4 | INTRODUCTION | 1 | 59 | [
"B59",
"B60",
"B61",
"B41",
"B62"
] | 17,567,608 | pmid-12887907|pmid-12887906|pmid-12359723|pmid-12453424|pmid-16785421|pmid-12359723|pmid-16818238|pmid-16916635|pmid-16785421 | The function of Rad54 as a Rad51 turnover factor is consistent with the absence of a Rad54 homolog in bacteria, because RecA is capable of turnover using its intrinsic ATPase activity. | [
"59",
"60",
"61",
"41",
"62"
] | 184 | 283 | 0 | false | The function of Rad54 as a Rad51 turnover factor is consistent with the absence of a Rad54 homolog in bacteria, because RecA is capable of turnover using its intrinsic ATPase activity. | [] | The function of Rad54 as a Rad51 turnover factor is consistent with the absence of a Rad54 homolog in bacteria, because RecA is capable of turnover using its intrinsic ATPase activity. | true | true | true | true | true | 46 |
5 | INTRODUCTION | 1 | 28 | [
"B28"
] | 17,567,608 | pmid-17302439|pmid-16818238|pmid-16818238|pmid-16818238|pmid-16818238 | Here, we analyzed the roles of both the Rad51 and Rad54 ATPase activities in turnover of the Rad51-dsDNA filament. | [
"28"
] | 114 | 284 | 0 | false | Here, we analyzed the roles of both the Rad51 and Rad54 ATPase activities in turnover of the Rad51-dsDNA filament. | [] | Here, we analyzed the roles of both the Rad51 and Rad54 ATPase activities in turnover of the Rad51-dsDNA filament. | true | true | true | true | true | 47 |
5 | INTRODUCTION | 1 | 28 | [
"B28"
] | 17,567,608 | pmid-17302439|pmid-16818238|pmid-16818238|pmid-16818238|pmid-16818238 | The results revealed a number of surprising features of the S. cerevisiae ATPase-deficient Rad51-K191R and Rad51-K191A proteins. | [
"28"
] | 128 | 285 | 0 | false | The results revealed a number of surprising features of the S. cerevisiae ATPase-deficient Rad51-K191R and Rad51-K191A proteins. | [] | The results revealed a number of surprising features of the S. cerevisiae ATPase-deficient Rad51-K191R and Rad51-K191A proteins. | true | true | true | true | true | 47 |
5 | INTRODUCTION | 1 | 28 | [
"B28"
] | 17,567,608 | pmid-17302439|pmid-16818238|pmid-16818238|pmid-16818238|pmid-16818238 | First, unexpectedly Rad51-K191A protein bound ATP, albeit with reduced affinity, similar to human Rad51-K133A (28). | [
"28"
] | 115 | 286 | 1 | false | First, unexpectedly Rad51-K191A protein bound ATP, albeit with reduced affinity, similar to human Rad51-K133A. | [
"28"
] | First, unexpectedly Rad51-K191A protein bound ATP, albeit with reduced affinity, similar to human Rad51-K133A. | true | true | true | true | true | 47 |
5 | INTRODUCTION | 1 | 28 | [
"B28"
] | 17,567,608 | pmid-17302439|pmid-16818238|pmid-16818238|pmid-16818238|pmid-16818238 | Second, the Rad51-K191R mutant protein displayed a DNA binding defect. | [
"28"
] | 70 | 287 | 0 | false | Second, the Rad51-K191R mutant protein displayed a DNA binding defect. | [] | Second, the Rad51-K191R mutant protein displayed a DNA binding defect. | true | true | true | true | true | 47 |
5 | INTRODUCTION | 1 | 28 | [
"B28"
] | 17,567,608 | pmid-17302439|pmid-16818238|pmid-16818238|pmid-16818238|pmid-16818238 | Third, once formed the Rad51-K191R-dsDNA complexes were exceptionally stable. | [
"28"
] | 77 | 288 | 0 | false | Third, once formed the Rad51-K191R-dsDNA complexes were exceptionally stable. | [] | Third, once formed the Rad51-K191R-dsDNA complexes were exceptionally stable. | true | true | true | true | true | 47 |
5 | INTRODUCTION | 1 | 28 | [
"B28"
] | 17,567,608 | pmid-17302439|pmid-16818238|pmid-16818238|pmid-16818238|pmid-16818238 | We demonstrate that the Rad54 ATPase activity was specifically enhanced in its interaction with the Rad51-dsDNA filament. | [
"28"
] | 121 | 289 | 0 | false | We demonstrate that the Rad54 ATPase activity was specifically enhanced in its interaction with the Rad51-dsDNA filament. | [] | We demonstrate that the Rad54 ATPase activity was specifically enhanced in its interaction with the Rad51-dsDNA filament. | true | true | true | true | true | 47 |
5 | INTRODUCTION | 1 | 28 | [
"B28"
] | 17,567,608 | pmid-17302439|pmid-16818238|pmid-16818238|pmid-16818238|pmid-16818238 | Efficient Rad51 turnover from dsDNA required both the Rad51 and Rad54 ATPase activities. | [
"28"
] | 88 | 290 | 0 | false | Efficient Rad51 turnover from dsDNA required both the Rad51 and Rad54 ATPase activities. | [] | Efficient Rad51 turnover from dsDNA required both the Rad51 and Rad54 ATPase activities. | true | true | true | true | true | 47 |
5 | INTRODUCTION | 1 | 28 | [
"B28"
] | 17,567,608 | pmid-17302439|pmid-16818238|pmid-16818238|pmid-16818238|pmid-16818238 | These results show that Rad51 is not a passive remodeling target of Rad54 and uncovered an intricate cooperation between the Rad51 and Rad54 ATPase activities in Rad51 turnover. | [
"28"
] | 177 | 291 | 0 | false | These results show that Rad51 is not a passive remodeling target of Rad54 and uncovered an intricate cooperation between the Rad51 and Rad54 ATPase activities in Rad51 turnover. | [] | These results show that Rad51 is not a passive remodeling target of Rad54 and uncovered an intricate cooperation between the Rad51 and Rad54 ATPase activities in Rad51 turnover. | true | true | true | true | true | 47 |
0 | DISCUSSION | 0 | null | null | 17,567,608 | pmid-15568977|pmid-10357855|pmid-11516927|pmid-10754547|pmid-15568977|pmid-12142524 | Rad51 and Rad54 are key DNA-dependent ATPases functioning in HR in eukaryotes. | null | 78 | 292 | 0 | false | null | null | Rad51 and Rad54 are key DNA-dependent ATPases functioning in HR in eukaryotes. | true | true | true | true | true | 48 |
0 | DISCUSSION | 0 | null | null | 17,567,608 | pmid-15568977|pmid-10357855|pmid-11516927|pmid-10754547|pmid-15568977|pmid-12142524 | Our analysis uncovered unexpected biochemical properties of the ATPase-deficient Rad51-K191R and Rad51-K191A mutant proteins. | null | 125 | 293 | 0 | false | null | null | Our analysis uncovered unexpected biochemical properties of the ATPase-deficient Rad51-K191R and Rad51-K191A mutant proteins. | true | true | true | true | true | 48 |
0 | DISCUSSION | 0 | null | null | 17,567,608 | pmid-15568977|pmid-10357855|pmid-11516927|pmid-10754547|pmid-15568977|pmid-12142524 | Kinetic analysis and experiments with different nucleotide cofactors revealed an intricate relationship between the Rad51 and Rad54 ATPase activities, demonstrating that both ATPase activities are required for efficient turnover of the Rad51-dsDNA filament. | null | 257 | 294 | 0 | false | null | null | Kinetic analysis and experiments with different nucleotide cofactors revealed an intricate relationship between the Rad51 and Rad54 ATPase activities, demonstrating that both ATPase activities are required for efficient turnover of the Rad51-dsDNA filament. | true | true | true | true | true | 48 |
1 | DISCUSSION | 1 | 72 | [
"B72",
"B14",
"B44",
"B44",
"B20",
"B28"
] | 17,567,608 | pmid-8066464|pmid-10357855|pmid-6329717|pmid-8910403|pmid-11030336|pmid-11030336|pmid-12192033|pmid-17302439 | The Walker A motif is a phosphate-binding loop that is found in many purine nucleotide-binding proteins including RecA and Rad51 (72). | [
"72",
"14",
"44",
"44",
"20",
"28"
] | 134 | 295 | 1 | false | The Walker A motif is a phosphate-binding loop that is found in many purine nucleotide-binding proteins including RecA and Rad51. | [
"72"
] | The Walker A motif is a phosphate-binding loop that is found in many purine nucleotide-binding proteins including RecA and Rad51. | true | true | true | true | true | 49 |
1 | DISCUSSION | 1 | 72 | [
"B72",
"B14",
"B44",
"B44",
"B20",
"B28"
] | 17,567,608 | pmid-8066464|pmid-10357855|pmid-6329717|pmid-8910403|pmid-11030336|pmid-11030336|pmid-12192033|pmid-17302439 | Mutations in the central lysine residue are often used to dissociate ATP binding and ATP hydrolysis, relying on an often untested assumption that the lysine to arginine substituted protein (e.g. | [
"72",
"14",
"44",
"44",
"20",
"28"
] | 194 | 296 | 0 | false | Mutations in the central lysine residue are often used to dissociate ATP binding and ATP hydrolysis, relying on an often untested assumption that the lysine to arginine substituted protein (e.g. | [] | Mutations in the central lysine residue are often used to dissociate ATP binding and ATP hydrolysis, relying on an often untested assumption that the lysine to arginine substituted protein (e.g. | true | true | true | true | true | 49 |
1 | DISCUSSION | 1 | 72 | [
"B72",
"B14",
"B44",
"B44",
"B20",
"B28"
] | 17,567,608 | pmid-8066464|pmid-10357855|pmid-6329717|pmid-8910403|pmid-11030336|pmid-11030336|pmid-12192033|pmid-17302439 | Rad51-K191R) binds but does not hydrolyze ATP, whereas the lysine to alanine substituted protein (e.g. | [
"72",
"14",
"44",
"44",
"20",
"28"
] | 102 | 297 | 0 | false | Rad51-K191R) binds but does not hydrolyze ATP, whereas the lysine to alanine substituted protein (e.g. | [] | Rad51-K191R) binds but does not hydrolyze ATP, whereas the lysine to alanine substituted protein (e.g. | true | true | true | true | true | 49 |
1 | DISCUSSION | 1 | 72 | [
"B72",
"B14",
"B44",
"B44",
"B20",
"B28"
] | 17,567,608 | pmid-8066464|pmid-10357855|pmid-6329717|pmid-8910403|pmid-11030336|pmid-11030336|pmid-12192033|pmid-17302439 | Rad51-K191A) cannot bind ATP. | [
"72",
"14",
"44",
"44",
"20",
"28"
] | 29 | 298 | 0 | false | Rad51-K191A) cannot bind ATP. | [] | Rad51-K191A) cannot bind ATP. | true | true | true | true | true | 49 |
1 | DISCUSSION | 1 | 72 | [
"B72",
"B14",
"B44",
"B44",
"B20",
"B28"
] | 17,567,608 | pmid-8066464|pmid-10357855|pmid-6329717|pmid-8910403|pmid-11030336|pmid-11030336|pmid-12192033|pmid-17302439 | Surprisingly, we find that both Rad51-K191R and Rad51-K191A mutant proteins bind ATP, albeit with reduced affinity compared with the wild-type protein (Table 1). | [
"72",
"14",
"44",
"44",
"20",
"28"
] | 161 | 299 | 0 | false | Surprisingly, we find that both Rad51-K191R and Rad51-K191A mutant proteins bind ATP, albeit with reduced affinity compared with the wild-type protein (Table 1). | [] | Surprisingly, we find that both Rad51-K191R and Rad51-K191A mutant proteins bind ATP, albeit with reduced affinity compared with the wild-type protein (Table 1). | true | true | true | true | true | 49 |
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