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
10
DISCUSSION
1
33
[ "b21", "b33" ]
17,099,236
pmid-16524591|pmid-8043575
As shown in the case of barnase-barstar (33), this may indicate that the E5-CRD/ImmE5 complex structure is very rigid, thereby suggesting the tight binding to the target tRNAs.
[ "21", "33" ]
176
1,200
1
false
As shown in the case of barnase-barstar, this may indicate that the E5-CRD/ImmE5 complex structure is very rigid, thereby suggesting the tight binding to the target tRNAs.
[ "33" ]
As shown in the case of barnase-barstar, this may indicate that the E5-CRD/ImmE5 complex structure is very rigid, thereby suggesting the tight binding to the target tRNAs.
true
true
true
true
true
209
10
DISCUSSION
1
21
[ "b21", "b33" ]
17,099,236
pmid-16524591|pmid-8043575
However, the free E5-CRD structure is rather flexible as shown in Figure 2.
[ "21", "33" ]
75
1,201
0
false
However, the free E5-CRD structure is rather flexible as shown in Figure 2.
[]
However, the free E5-CRD structure is rather flexible as shown in Figure 2.
true
true
true
true
true
209
10
DISCUSSION
1
21
[ "b21", "b33" ]
17,099,236
pmid-16524591|pmid-8043575
The interaction of E5-CRD and ImmE5 was realized mainly by the electrostatic interaction between the positive charges on E5-CRD and the negative charges on ImmE5.
[ "21", "33" ]
162
1,202
0
false
The interaction of E5-CRD and ImmE5 was realized mainly by the electrostatic interaction between the positive charges on E5-CRD and the negative charges on ImmE5.
[]
The interaction of E5-CRD and ImmE5 was realized mainly by the electrostatic interaction between the positive charges on E5-CRD and the negative charges on ImmE5.
true
true
true
true
true
209
10
DISCUSSION
1
21
[ "b21", "b33" ]
17,099,236
pmid-16524591|pmid-8043575
In addition to the observation on this binding mode by Luna-Chávez et al., we found that 12 water molecules interacted with the main chains or side chains of ImmE5 and E5-CRD through the hydrogen bonds resulting in the filling of the gap between the two proteins; this may contribute to their tight binding.
[ "21", "33" ]
307
1,203
0
false
In addition to the observation on this binding mode by Luna-Chávez et al., we found that 12 water molecules interacted with the main chains or side chains of ImmE5 and E5-CRD through the hydrogen bonds resulting in the filling of the gap between the two proteins; this may contribute to their tight binding.
[]
In addition to the observation on this binding mode by Luna-Chávez et al., we found that 12 water molecules interacted with the main chains or side chains of ImmE5 and E5-CRD through the hydrogen bonds resulting in the filling of the gap between the two proteins; this may contribute to their tight binding.
true
true
true
true
true
209
10
DISCUSSION
1
21
[ "b21", "b33" ]
17,099,236
pmid-16524591|pmid-8043575
As determined in a preliminary modeling study on E5-CRD and the tRNA molecule, an anticodon loop fits in the pocket within which are located a long loop (Phe60–Pro73) comprising two short strands and a helix of ImmE5 (Figure 6).
[ "21", "33" ]
228
1,204
0
false
As determined in a preliminary modeling study on E5-CRD and the tRNA molecule, an anticodon loop fits in the pocket within which are located a long loop (Phe60–Pro73) comprising two short strands and a helix of ImmE5 (Figure 6).
[]
As determined in a preliminary modeling study on E5-CRD and the tRNA molecule, an anticodon loop fits in the pocket within which are located a long loop (Phe60–Pro73) comprising two short strands and a helix of ImmE5 (Figure 6).
true
true
true
true
true
209
10
DISCUSSION
1
21
[ "b21", "b33" ]
17,099,236
pmid-16524591|pmid-8043575
Based on this conformation of the interaction of E5-CRD/ImmE5, we considered that the long loop region in ImmE5 may mimic the anticodon loop of a tRNA.
[ "21", "33" ]
151
1,205
0
false
Based on this conformation of the interaction of E5-CRD/ImmE5, we considered that the long loop region in ImmE5 may mimic the anticodon loop of a tRNA.
[]
Based on this conformation of the interaction of E5-CRD/ImmE5, we considered that the long loop region in ImmE5 may mimic the anticodon loop of a tRNA.
true
true
true
true
true
209
10
DISCUSSION
1
21
[ "b21", "b33" ]
17,099,236
pmid-16524591|pmid-8043575
Additionally, the basic residues Lys25, Arg33 and Lys60, which are essential for the catalytic activity of E5-CRD are in contact with the acidic residues Asp51 and Asp94 in ImmE5.
[ "21", "33" ]
179
1,206
0
false
Additionally, the basic residues Lys25, Arg33 and Lys60, which are essential for the catalytic activity of E5-CRD are in contact with the acidic residues Asp51 and Asp94 in ImmE5.
[]
Additionally, the basic residues Lys25, Arg33 and Lys60, which are essential for the catalytic activity of E5-CRD are in contact with the acidic residues Asp51 and Asp94 in ImmE5.
true
true
true
true
true
209
10
DISCUSSION
1
21
[ "b21", "b33" ]
17,099,236
pmid-16524591|pmid-8043575
When we superposed the E5-CRD/ImmE5 complex structure onto the E5-CRD/dGpdUp complex structure, the positions of Asp51 and Asp94 corresponded with those of the two phosphates of dGpdUp (Figure 7).
[ "21", "33" ]
196
1,207
0
false
When we superposed the E5-CRD/ImmE5 complex structure onto the E5-CRD/dGpdUp complex structure, the positions of Asp51 and Asp94 corresponded with those of the two phosphates of dGpdUp (Figure 7).
[]
When we superposed the E5-CRD/ImmE5 complex structure onto the E5-CRD/dGpdUp complex structure, the positions of Asp51 and Asp94 corresponded with those of the two phosphates of dGpdUp (Figure 7).
true
true
true
true
true
209
10
DISCUSSION
1
21
[ "b21", "b33" ]
17,099,236
pmid-16524591|pmid-8043575
This suggests that the acidic residues in ImmE5 mimic the phosphates in the anticodon; thus, ImmE5 inhibits the E5-CRD activity by mimicking the binding mode of the tRNA anticodon loop.
[ "21", "33" ]
185
1,208
0
false
This suggests that the acidic residues in ImmE5 mimic the phosphates in the anticodon; thus, ImmE5 inhibits the E5-CRD activity by mimicking the binding mode of the tRNA anticodon loop.
[]
This suggests that the acidic residues in ImmE5 mimic the phosphates in the anticodon; thus, ImmE5 inhibits the E5-CRD activity by mimicking the binding mode of the tRNA anticodon loop.
true
true
true
true
true
209
11
DISCUSSION
0
null
null
17,099,236
null
As described above, dGpdUp binds to E5-CRD using ring–ring interactions and hydrogen bonds at base rings in a manner similar to the Watson–Crick-type interaction (Figure 3A and C).
null
180
1,209
0
false
null
null
As described above, dGpdUp binds to E5-CRD using ring–ring interactions and hydrogen bonds at base rings in a manner similar to the Watson–Crick-type interaction (Figure 3A and C).
true
true
true
true
true
210
11
DISCUSSION
0
null
null
17,099,236
null
Thus, it is very likely that the E5-CRD/dGpdUp binding mode mimics an mRNA–tRNA interaction.
null
92
1,210
0
false
null
null
Thus, it is very likely that the E5-CRD/dGpdUp binding mode mimics an mRNA–tRNA interaction.
true
true
true
true
true
210
11
DISCUSSION
0
null
null
17,099,236
null
If E5-CRD mimics mRNA while binding to tRNA and ImmE5 mimics tRNA while binding to E5-CRD, we speculate that the molecular recognition mode of the protein–protein interaction in E5-CRD/ImmE5 may be the culmination of the molecular evolution originating from the mRNA–tRNA interaction.
null
284
1,211
0
false
null
null
If E5-CRD mimics mRNA while binding to tRNA and ImmE5 mimics tRNA while binding to E5-CRD, we speculate that the molecular recognition mode of the protein–protein interaction in E5-CRD/ImmE5 may be the culmination of the molecular evolution originating from the mRNA–tRNA interaction.
true
true
true
true
true
210
12
DISCUSSION
0
null
null
17,099,236
null
In the evolutionary process, initially, E5-CRD could replace the mRNA interacting with the tRNA by means of Trp102 and Asp105–Arg107 that mimicked the nucleotide base stacking with the G–U nucleotides of tRNA.
null
209
1,212
0
false
null
null
In the evolutionary process, initially, E5-CRD could replace the mRNA interacting with the tRNA by means of Trp102 and Asp105–Arg107 that mimicked the nucleotide base stacking with the G–U nucleotides of tRNA.
true
true
true
true
true
211
12
DISCUSSION
0
null
null
17,099,236
null
Trp102 and Asp105–Arg107 in E5-CRD mimicked the nucleotide bases in the mRNA, suggesting the interaction of Trp102 and Asp105–Arg107 with G–U.
null
142
1,213
0
false
null
null
Trp102 and Asp105–Arg107 in E5-CRD mimicked the nucleotide bases in the mRNA, suggesting the interaction of Trp102 and Asp105–Arg107 with G–U.
true
true
true
true
true
211
12
DISCUSSION
0
null
null
17,099,236
null
Subsequently, additional interactions between the phosphate groups of the substrate and basic residues in E5-CRD were established to stabilize the binding (the interactions between blue-colored residues and dGpdUp in Figure 7).
null
227
1,214
0
false
null
null
Subsequently, additional interactions between the phosphate groups of the substrate and basic residues in E5-CRD were established to stabilize the binding (the interactions between blue-colored residues and dGpdUp in Figure 7).
true
true
true
true
true
211
12
DISCUSSION
0
null
null
17,099,236
null
Then, ImmE5 could replace the tRNA to interact with E5-CRD; the guanine base was replaced by Phe60 of ImmE5, and two phosphates were replaced by Asp51 and Asp94.
null
161
1,215
0
false
null
null
Then, ImmE5 could replace the tRNA to interact with E5-CRD; the guanine base was replaced by Phe60 of ImmE5, and two phosphates were replaced by Asp51 and Asp94.
true
true
true
true
true
211
12
DISCUSSION
0
null
null
17,099,236
null
Due to this replacement, the hydrogen bonds and the ring interactions between dGpdUp and the residues in E5-CRD are almost precisely retained by the residues in ImmE5 and E5-CRD at the corresponding positions.
null
209
1,216
0
false
null
null
Due to this replacement, the hydrogen bonds and the ring interactions between dGpdUp and the residues in E5-CRD are almost precisely retained by the residues in ImmE5 and E5-CRD at the corresponding positions.
true
true
true
true
true
211
0
INTRODUCTION
1
1–5
[ "B1 B2 B3 B4 B5" ]
17,626,046
pmid-12683970|pmid-12868601|NA|pmid-16015595|pmid-15016989|pmid-8945517|pmid-9922177
In the higher eukaryotes frequently more than 90% of the DNA does not code for functional proteins or RNA.
[ "1–5" ]
106
1,217
0
false
In the higher eukaryotes frequently more than 90% of the DNA does not code for functional proteins or RNA.
[]
In the higher eukaryotes frequently more than 90% of the DNA does not code for functional proteins or RNA.
true
true
true
true
true
212
0
INTRODUCTION
1
1–5
[ "B1 B2 B3 B4 B5" ]
17,626,046
pmid-12683970|pmid-12868601|NA|pmid-16015595|pmid-15016989|pmid-8945517|pmid-9922177
Much of this DNA has originated from the action of mobile genetic elements, mostly retrotransposons that propagate in a copy-and-paste mechanism via an RNA intermediate.
[ "1–5" ]
169
1,218
0
false
Much of this DNA has originated from the action of mobile genetic elements, mostly retrotransposons that propagate in a copy-and-paste mechanism via an RNA intermediate.
[]
Much of this DNA has originated from the action of mobile genetic elements, mostly retrotransposons that propagate in a copy-and-paste mechanism via an RNA intermediate.
true
true
true
true
true
212
0
INTRODUCTION
1
1–5
[ "B1 B2 B3 B4 B5" ]
17,626,046
pmid-12683970|pmid-12868601|NA|pmid-16015595|pmid-15016989|pmid-8945517|pmid-9922177
While these elements can be viewed as molecular parasites that are in an evolutionary race with their host genome, they can also be regarded as essential genomic components for slowly reproducing species to adapt to a changing environment.
[ "1–5" ]
239
1,219
0
false
While these elements can be viewed as molecular parasites that are in an evolutionary race with their host genome, they can also be regarded as essential genomic components for slowly reproducing species to adapt to a changing environment.
[]
While these elements can be viewed as molecular parasites that are in an evolutionary race with their host genome, they can also be regarded as essential genomic components for slowly reproducing species to adapt to a changing environment.
true
true
true
true
true
212
0
INTRODUCTION
1
1–5
[ "B1 B2 B3 B4 B5" ]
17,626,046
pmid-12683970|pmid-12868601|NA|pmid-16015595|pmid-15016989|pmid-8945517|pmid-9922177
They generate allelic heterogeneity and create new possibilities for genetic recombination, increasing genomic fluidity (1–5).
[ "1–5" ]
126
1,220
1
false
They generate allelic heterogeneity and create new possibilities for genetic recombination, increasing genomic fluidity.
[ "1–5" ]
They generate allelic heterogeneity and create new possibilities for genetic recombination, increasing genomic fluidity.
true
true
true
true
true
212
1
INTRODUCTION
1
3
[ "B3", "B6 B7 B8" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
Mobile genetic elements integrate into new genomic locations in two fundamentally different ways.
[ "3", "6–8" ]
97
1,221
0
false
Mobile genetic elements integrate into new genomic locations in two fundamentally different ways.
[]
Mobile genetic elements integrate into new genomic locations in two fundamentally different ways.
true
true
true
true
true
213
1
INTRODUCTION
1
3
[ "B3", "B6 B7 B8" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
DNA transposons and retrotransposons with long terminal repeats (LTR retrotransposons) use a transposase/integrase to insert a double-stranded DNA copy of the element at the target site.
[ "3", "6–8" ]
186
1,222
0
false
DNA transposons and retrotransposons with long terminal repeats (LTR retrotransposons) use a transposase/integrase to insert a double-stranded DNA copy of the element at the target site.
[]
DNA transposons and retrotransposons with long terminal repeats (LTR retrotransposons) use a transposase/integrase to insert a double-stranded DNA copy of the element at the target site.
true
true
true
true
true
213
1
INTRODUCTION
1
3
[ "B3", "B6 B7 B8" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
In this case, no DNA synthesis takes place at the site of integration.
[ "3", "6–8" ]
70
1,223
0
false
In this case, no DNA synthesis takes place at the site of integration.
[]
In this case, no DNA synthesis takes place at the site of integration.
true
true
true
true
true
213
1
INTRODUCTION
1
3
[ "B3", "B6 B7 B8" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
In contrast, non-LTR retrotransposons use a mechanism called target-primed reverse transcription (3).
[ "3", "6–8" ]
101
1,224
1
false
In contrast, non-LTR retrotransposons use a mechanism called target-primed reverse transcription.
[ "3" ]
In contrast, non-LTR retrotransposons use a mechanism called target-primed reverse transcription.
true
true
true
true
true
213
1
INTRODUCTION
1
3
[ "B3", "B6 B7 B8" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
This process is initiated by a targeting endonuclease, which specifically binds to the site of genomic integration.
[ "3", "6–8" ]
115
1,225
0
false
This process is initiated by a targeting endonuclease, which specifically binds to the site of genomic integration.
[]
This process is initiated by a targeting endonuclease, which specifically binds to the site of genomic integration.
true
true
true
true
true
213
1
INTRODUCTION
1
3
[ "B3", "B6 B7 B8" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
It nicks one strand of the DNA and creates a free 3′ hydroxyl end, which is then used as a primer for reverse transcription of the retrotransposon RNA at the site of integration.
[ "3", "6–8" ]
178
1,226
0
false
It nicks one strand of the DNA and creates a free 3′ hydroxyl end, which is then used as a primer for reverse transcription of the retrotransposon RNA at the site of integration.
[]
It nicks one strand of the DNA and creates a free 3′ hydroxyl end, which is then used as a primer for reverse transcription of the retrotransposon RNA at the site of integration.
true
true
true
true
true
213
1
INTRODUCTION
1
3
[ "B3", "B6 B7 B8" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
Endonuclease and reverse transcriptase are two domains of a single retrotransposon-encoded protein.
[ "3", "6–8" ]
99
1,227
0
false
Endonuclease and reverse transcriptase are two domains of a single retrotransposon-encoded protein.
[]
Endonuclease and reverse transcriptase are two domains of a single retrotransposon-encoded protein.
true
true
true
true
true
213
1
INTRODUCTION
1
6–8
[ "B3", "B6 B7 B8" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
They are thought to rely on the assistance of ‘host’-encoded proteins to complete the integration process (6–8).
[ "3", "6–8" ]
112
1,228
1
false
They are thought to rely on the assistance of ‘host’-encoded proteins to complete the integration process.
[ "6–8" ]
They are thought to rely on the assistance of ‘host’-encoded proteins to complete the integration process.
true
true
true
true
true
213
2
INTRODUCTION
1
9
[ "B9", "B10" ]
17,626,046
pmid-16093679|pmid-10838565|pmid-15274918
Most non-LTR retrotransposons are APE-type non-LTR retrotransposons (9).
[ "9", "10" ]
72
1,229
1
false
Most non-LTR retrotransposons are APE-type non-LTR retrotransposons.
[ "9" ]
Most non-LTR retrotransposons are APE-type non-LTR retrotransposons.
true
true
true
true
true
214
2
INTRODUCTION
1
9
[ "B9", "B10" ]
17,626,046
pmid-16093679|pmid-10838565|pmid-15274918
Their targeting endonuclease belongs to a family of metal-dependent phosphohydrolases that includes nucleases like DNaseI (PDB-ID: 1dnk), APE1 (PDB-ID: 1dew), Exo III (PDB-ID: 1ako) and CdtB (PDB-ID: 1sr4) but also sugar phosphatases like I5PP (PDB-ID: 1i9z) and phospholipases like SmcL (PDB-ID: 1zwx) and Bc-SMase (PDB-ID: 2ddt).
[ "9", "10" ]
331
1,230
0
false
Their targeting endonuclease belongs to a family of metal-dependent phosphohydrolases that includes nucleases like DNaseI (PDB-ID: 1dnk), APE1 (PDB-ID: 1dew), Exo III (PDB-ID: 1ako) and CdtB (PDB-ID: 1sr4) but also sugar phosphatases like I5PP and phospholipases like SmcL (PDB-ID: 1zwx) and Bc-SMase (PDB-ID: 2ddt).
[ "PDB-ID: 1i9z" ]
Their targeting endonuclease belongs to a family of metal-dependent phosphohydrolases that includes nucleases like DNaseI (PDB-ID: 1dnk), APE1 (PDB-ID: 1dew), Exo III (PDB-ID: 1ako) and CdtB (PDB-ID: 1sr4) but also sugar phosphatases like I5PP and phospholipases like SmcL (PDB-ID: 1zwx) and Bc-SMase (PDB-ID: 2ddt).
true
true
true
true
true
214
2
INTRODUCTION
1
10
[ "B9", "B10" ]
17,626,046
pmid-16093679|pmid-10838565|pmid-15274918
Members of this family share the same protein scaffold and the same catalytic residues, but a variation of the connecting surface loops has allowed them to develop quite diverse substrate specificities (10).
[ "9", "10" ]
207
1,231
1
false
Members of this family share the same protein scaffold and the same catalytic residues, but a variation of the connecting surface loops has allowed them to develop quite diverse substrate specificities.
[ "10" ]
Members of this family share the same protein scaffold and the same catalytic residues, but a variation of the connecting surface loops has allowed them to develop quite diverse substrate specificities.
true
true
true
true
true
214
3
INTRODUCTION
1
9
[ "B9", "B11", "B12", "B13", "B14", "B15", "B16 B17 B18", "B19", "B20", "B21 B22 B23 B24" ]
17,626,046
pmid-16093679|pmid-2447482|pmid-2550791|pmid-10648607|pmid-9482842|pmid-1662412|pmid-12176319|pmid-12176320|NA|pmid-9922177|pmid-8945517|pmid-16728505|pmid-16735504|pmid-16936727|pmid-9260521|pmid-16093679|pmid-12006980|pmid-16490214
Under the pressure to survive in their respective host species non-LTR retrotransposons have evolved different strategies (9).
[ "9", "11", "12", "13", "14", "15", "16–18", "19", "20", "21–24" ]
126
1,232
1
false
Under the pressure to survive in their respective host species non-LTR retrotransposons have evolved different strategies.
[ "9" ]
Under the pressure to survive in their respective host species non-LTR retrotransposons have evolved different strategies.
true
true
true
true
true
215
3
INTRODUCTION
1
11
[ "B9", "B11", "B12", "B13", "B14", "B15", "B16 B17 B18", "B19", "B20", "B21 B22 B23 B24" ]
17,626,046
pmid-16093679|pmid-2447482|pmid-2550791|pmid-10648607|pmid-9482842|pmid-1662412|pmid-12176319|pmid-12176320|NA|pmid-9922177|pmid-8945517|pmid-16728505|pmid-16735504|pmid-16936727|pmid-9260521|pmid-16093679|pmid-12006980|pmid-16490214
Stringent elements like R1Bm from Bombyx mori (11) and Tx1L from Xenopus laevis (12) encode highly specific targeting endonucleases (13,14).
[ "9", "11", "12", "13", "14", "15", "16–18", "19", "20", "21–24" ]
140
1,233
1
false
Stringent elements like R1Bm from Bombyx mori and Tx1L from Xenopus laevis encode highly specific targeting endonucleases.
[ "11", "12", "13,14" ]
Stringent elements like R1Bm from Bombyx mori and Tx1L from Xenopus laevis encode highly specific targeting endonucleases.
true
true
true
true
true
215
3
INTRODUCTION
1
9
[ "B9", "B11", "B12", "B13", "B14", "B15", "B16 B17 B18", "B19", "B20", "B21 B22 B23 B24" ]
17,626,046
pmid-16093679|pmid-2447482|pmid-2550791|pmid-10648607|pmid-9482842|pmid-1662412|pmid-12176319|pmid-12176320|NA|pmid-9922177|pmid-8945517|pmid-16728505|pmid-16735504|pmid-16936727|pmid-9260521|pmid-16093679|pmid-12006980|pmid-16490214
They integrate into unique genomic locations (a specific sequence within 28S rDNA for R1Bm or within the apparent DNA transposon Tx1D for Tx1L) where they do very little or no damage to the host.
[ "9", "11", "12", "13", "14", "15", "16–18", "19", "20", "21–24" ]
195
1,234
0
false
They integrate into unique genomic locations (a specific sequence within 28S rDNA for R1Bm or within the apparent DNA transposon Tx1D for Tx1L) where they do very little or no damage to the host.
[]
They integrate into unique genomic locations (a specific sequence within 28S rDNA for R1Bm or within the apparent DNA transposon Tx1D for Tx1L) where they do very little or no damage to the host.
true
true
true
true
true
215
3
INTRODUCTION
1
15
[ "B9", "B11", "B12", "B13", "B14", "B15", "B16 B17 B18", "B19", "B20", "B21 B22 B23 B24" ]
17,626,046
pmid-16093679|pmid-2447482|pmid-2550791|pmid-10648607|pmid-9482842|pmid-1662412|pmid-12176319|pmid-12176320|NA|pmid-9922177|pmid-8945517|pmid-16728505|pmid-16735504|pmid-16936727|pmid-9260521|pmid-16093679|pmid-12006980|pmid-16490214
Promiscuous elements like the human LINE-1 (L1) element (15) may integrate into several hundred thousand genomic locations.
[ "9", "11", "12", "13", "14", "15", "16–18", "19", "20", "21–24" ]
123
1,235
1
false
Promiscuous elements like the human LINE-1 (L1) element may integrate into several hundred thousand genomic locations.
[ "15" ]
Promiscuous elements like the human LINE-1 element may integrate into several hundred thousand genomic locations.
true
true
true
true
true
215
3
INTRODUCTION
1
9
[ "B9", "B11", "B12", "B13", "B14", "B15", "B16 B17 B18", "B19", "B20", "B21 B22 B23 B24" ]
17,626,046
pmid-16093679|pmid-2447482|pmid-2550791|pmid-10648607|pmid-9482842|pmid-1662412|pmid-12176319|pmid-12176320|NA|pmid-9922177|pmid-8945517|pmid-16728505|pmid-16735504|pmid-16936727|pmid-9260521|pmid-16093679|pmid-12006980|pmid-16490214
They have a rather short integration-site consensus [5′-TTTT/AA-3′ for L1 (16–18)] that is nicked by the respective targeting endonuclease (19,20).
[ "9", "11", "12", "13", "14", "15", "16–18", "19", "20", "21–24" ]
147
1,236
0
false
They have a rather short integration-site consensus that is nicked by the respective targeting endonuclease.
[ "5′-TTTT/AA-3′ for L1 (16–18)", "19,20" ]
They have a rather short integration-site consensus that is nicked by the respective targeting endonuclease.
true
true
true
true
true
215
3
INTRODUCTION
1
21–24
[ "B9", "B11", "B12", "B13", "B14", "B15", "B16 B17 B18", "B19", "B20", "B21 B22 B23 B24" ]
17,626,046
pmid-16093679|pmid-2447482|pmid-2550791|pmid-10648607|pmid-9482842|pmid-1662412|pmid-12176319|pmid-12176320|NA|pmid-9922177|pmid-8945517|pmid-16728505|pmid-16735504|pmid-16936727|pmid-9260521|pmid-16093679|pmid-12006980|pmid-16490214
The host limits the spread of such elements by transcriptional and post-transcriptional silencing mechanisms that reduce activity to tolerable levels (21–24).
[ "9", "11", "12", "13", "14", "15", "16–18", "19", "20", "21–24" ]
158
1,237
1
false
The host limits the spread of such elements by transcriptional and post-transcriptional silencing mechanisms that reduce activity to tolerable levels.
[ "21–24" ]
The host limits the spread of such elements by transcriptional and post-transcriptional silencing mechanisms that reduce activity to tolerable levels.
true
true
true
true
true
215
4
INTRODUCTION
1
13
[ "B13", "B14", "B19", "B25", "B26" ]
17,626,046
pmid-10648607|pmid-9482842|pmid-9922177|pmid-11823433|pmid-12644555|pmid-15247245|pmid-9482842|pmid-15274918
Clearly, the respective endonucleases play a major role in target site selection (13,14,19,25).
[ "13", "14", "19", "25", "26" ]
95
1,238
0
false
Clearly, the respective endonucleases play a major role in target site selection.
[ "13,14,19,25" ]
Clearly, the respective endonucleases play a major role in target site selection.
true
true
true
true
true
216
4
INTRODUCTION
1
13
[ "B13", "B14", "B19", "B25", "B26" ]
17,626,046
pmid-10648607|pmid-9482842|pmid-9922177|pmid-11823433|pmid-12644555|pmid-15247245|pmid-9482842|pmid-15274918
The intriguing question of how different targeting endonucleases recognize the DNA substrate and how easily new specificities can arise in the course of evolution remains open.
[ "13", "14", "19", "25", "26" ]
176
1,239
0
false
The intriguing question of how different targeting endonucleases recognize the DNA substrate and how easily new specificities can arise in the course of evolution remains open.
[]
The intriguing question of how different targeting endonucleases recognize the DNA substrate and how easily new specificities can arise in the course of evolution remains open.
true
true
true
true
true
216
4
INTRODUCTION
1
26
[ "B13", "B14", "B19", "B25", "B26" ]
17,626,046
pmid-10648607|pmid-9482842|pmid-9922177|pmid-11823433|pmid-12644555|pmid-15247245|pmid-9482842|pmid-15274918
There are indications that retrotransposons can evolve back and forth between a stringent and a promiscuous mode-of-action (26) and the ability to manipulate and design target specificity would be a crucial step in converting non-LTR retrotransposons into a genetic tool.
[ "13", "14", "19", "25", "26" ]
271
1,240
1
false
There are indications that retrotransposons can evolve back and forth between a stringent and a promiscuous mode-of-action and the ability to manipulate and design target specificity would be a crucial step in converting non-LTR retrotransposons into a genetic tool.
[ "26" ]
There are indications that retrotransposons can evolve back and forth between a stringent and a promiscuous mode-of-action and the ability to manipulate and design target specificity would be a crucial step in converting non-LTR retrotransposons into a genetic tool.
true
true
true
true
true
216
5
INTRODUCTION
1
27
[ "B27" ]
17,626,046
pmid-15274918|pmid-11700292|pmid-15578988|pmid-17124176|pmid-16093679|pmid-15274918
Previously, we described the crystal structure of the human L1 endonuclease (L1-EN) (27).
[ "27" ]
89
1,241
1
false
Previously, we described the crystal structure of the human L1 endonuclease (L1-EN).
[ "27" ]
Previously, we described the crystal structure of the human L1 endonuclease (L1-EN).
true
true
true
true
true
217
5
INTRODUCTION
1
27
[ "B27" ]
17,626,046
pmid-15274918|pmid-11700292|pmid-15578988|pmid-17124176|pmid-16093679|pmid-15274918
Based on structure comparisons and sequence alignments we suggested that the prominent βB6–βB5 hairpin loop may insert into the DNA minor groove and may be particularly important for recognizing the DNA target.
[ "27" ]
210
1,242
0
false
Based on structure comparisons and sequence alignments we suggested that the prominent βB6–βB5 hairpin loop may insert into the DNA minor groove and may be particularly important for recognizing the DNA target.
[]
Based on structure comparisons and sequence alignments we suggested that the prominent βB6–βB5 hairpin loop may insert into the DNA minor groove and may be particularly important for recognizing the DNA target.
true
true
true
true
true
217
5
INTRODUCTION
1
27
[ "B27" ]
17,626,046
pmid-15274918|pmid-11700292|pmid-15578988|pmid-17124176|pmid-16093679|pmid-15274918
Here, we combine a mutational approach (specific point mutants and entire loop grafts) with structural and dynamic analyses.
[ "27" ]
124
1,243
0
false
Here, we combine a mutational approach (specific point mutants and entire loop grafts) with structural and dynamic analyses.
[]
Here, we combine a mutational approach (specific point mutants and entire loop grafts) with structural and dynamic analyses.
true
true
true
true
true
217
5
INTRODUCTION
1
27
[ "B27" ]
17,626,046
pmid-15274918|pmid-11700292|pmid-15578988|pmid-17124176|pmid-16093679|pmid-15274918
We determine minimal size and structural features of the DNA target and we show that size and flexibility of the βB6–βB5 hairpin loop are crucial for activity.
[ "27" ]
159
1,244
0
false
We determine minimal size and structural features of the DNA target and we show that size and flexibility of the βB6–βB5 hairpin loop are crucial for activity.
[]
We determine minimal size and structural features of the DNA target and we show that size and flexibility of the βB6–βB5 hairpin loop are crucial for activity.
true
true
true
true
true
217
5
INTRODUCTION
1
27
[ "B27" ]
17,626,046
pmid-15274918|pmid-11700292|pmid-15578988|pmid-17124176|pmid-16093679|pmid-15274918
Variation of the loop sequence results in an altered DNA nicking profile including novel sites.
[ "27" ]
95
1,245
0
false
Variation of the loop sequence results in an altered DNA nicking profile including novel sites.
[]
Variation of the loop sequence results in an altered DNA nicking profile including novel sites.
true
true
true
true
true
217
5
INTRODUCTION
1
27
[ "B27" ]
17,626,046
pmid-15274918|pmid-11700292|pmid-15578988|pmid-17124176|pmid-16093679|pmid-15274918
This indicates that the engineering of novel specificities may ultimately be feasible.
[ "27" ]
86
1,246
0
false
This indicates that the engineering of novel specificities may ultimately be feasible.
[]
This indicates that the engineering of novel specificities may ultimately be feasible.
true
true
true
true
true
217
0
DISCUSSION
1
20
[ "B20", "B19" ]
17,626,046
pmid-12683970|pmid-12868601|NA|pmid-16015595|pmid-15016989|pmid-8945517|pmid-9922177
DNA target specificity of L1-EN has been studied before with plasmid DNA (20) and with special DNA duplexes that contained a symmetric junction of two T-tracts (19).
[ "20", "19" ]
165
1,247
1
false
DNA target specificity of L1-EN has been studied before with plasmid DNA and with special DNA duplexes that contained a symmetric junction of two T-tracts.
[ "20", "19" ]
DNA target specificity of L1-EN has been studied before with plasmid DNA and with special DNA duplexes that contained a symmetric junction of two T-tracts.
true
true
true
true
true
218
0
DISCUSSION
1
20
[ "B20", "B19" ]
17,626,046
pmid-12683970|pmid-12868601|NA|pmid-16015595|pmid-15016989|pmid-8945517|pmid-9922177
The present study confirms such junctions to be ideal nicking substrates for L1-EN and corroborates the importance of the DNA structure for molecular recognition.
[ "20", "19" ]
162
1,248
0
false
The present study confirms such junctions to be ideal nicking substrates for L1-EN and corroborates the importance of the DNA structure for molecular recognition.
[]
The present study confirms such junctions to be ideal nicking substrates for L1-EN and corroborates the importance of the DNA structure for molecular recognition.
true
true
true
true
true
218
0
DISCUSSION
1
20
[ "B20", "B19" ]
17,626,046
pmid-12683970|pmid-12868601|NA|pmid-16015595|pmid-15016989|pmid-8945517|pmid-9922177
We extend the previous analyses to asymmetric DNA targets and determine minimal substrate requirements for the flanking upstream and downstream sequences.
[ "20", "19" ]
154
1,249
0
false
We extend the previous analyses to asymmetric DNA targets and determine minimal substrate requirements for the flanking upstream and downstream sequences.
[]
We extend the previous analyses to asymmetric DNA targets and determine minimal substrate requirements for the flanking upstream and downstream sequences.
true
true
true
true
true
218
0
DISCUSSION
1
20
[ "B20", "B19" ]
17,626,046
pmid-12683970|pmid-12868601|NA|pmid-16015595|pmid-15016989|pmid-8945517|pmid-9922177
Furthermore, we look at the nicking specificity of L1-EN on more general DNA substrates and compare it to the integration specificity of L1 elements in vivo.
[ "20", "19" ]
157
1,250
0
false
Furthermore, we look at the nicking specificity of L1-EN on more general DNA substrates and compare it to the integration specificity of L1 elements in vivo.
[]
Furthermore, we look at the nicking specificity of L1-EN on more general DNA substrates and compare it to the integration specificity of L1 elements in vivo.
true
true
true
true
true
218
1
DISCUSSION
1
19
[ "B19", "B42", "B42" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
We find that with unstrained duplex DNA, L1-EN requires a minimum of 5 bp upstream and 3 bp downstream of the target site for efficient target recognition.
[ "19", "42", "42" ]
155
1,251
0
false
We find that with unstrained duplex DNA, L1-EN requires a minimum of 5 bp upstream and 3 bp downstream of the target site for efficient target recognition.
[]
We find that with unstrained duplex DNA, L1-EN requires a minimum of 5 bp upstream and 3 bp downstream of the target site for efficient target recognition.
true
true
true
true
true
219
1
DISCUSSION
1
19
[ "B19", "B42", "B42" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
On the upstream duplex L1-EN recognizes mainly the T-tract (A-tract) geometry (19) that is primarily characterized by its very narrow minor groove (42).
[ "19", "42", "42" ]
152
1,252
1
false
On the upstream duplex L1-EN recognizes mainly the T-tract (A-tract) geometry that is primarily characterized by its very narrow minor groove.
[ "19", "42" ]
On the upstream duplex L1-EN recognizes mainly the T-tract (A-tract) geometry that is primarily characterized by its very narrow minor groove.
true
true
true
true
true
219
1
DISCUSSION
1
19
[ "B19", "B42", "B42" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
Downstream, the 3 bp are just enough to form an independent stem.
[ "19", "42", "42" ]
65
1,253
0
false
Downstream, the 3 bp are just enough to form an independent stem.
[]
Downstream, the 3 bp are just enough to form an independent stem.
true
true
true
true
true
219
1
DISCUSSION
1
42
[ "B19", "B42", "B42" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
In the case of a T-A junction following the T-tract (poly(T)-A junction), the downstream adenine is not stacked on the upstream thymidine (42) and thus, the downstream stem can more easily be bent away with an associated widening of the minor groove.
[ "19", "42", "42" ]
250
1,254
1
false
In the case of a T-A junction following the T-tract (poly(T)-A junction), the downstream adenine is not stacked on the upstream thymidine and thus, the downstream stem can more easily be bent away with an associated widening of the minor groove.
[ "42" ]
In the case of a T-A junction following the T-tract (poly(T)-A junction), the downstream adenine is not stacked on the upstream thymidine and thus, the downstream stem can more easily be bent away with an associated widening of the minor groove.
true
true
true
true
true
219
1
DISCUSSION
1
19
[ "B19", "B42", "B42" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
Most likely, this local flexibility is a feature that is recognized by L1-EN in addition to the narrow minor groove of the T-tract, leading to the enhanced nicking efficiency observed at the junction.
[ "19", "42", "42" ]
200
1,255
0
false
Most likely, this local flexibility is a feature that is recognized by L1-EN in addition to the narrow minor groove of the T-tract, leading to the enhanced nicking efficiency observed at the junction.
[]
Most likely, this local flexibility is a feature that is recognized by L1-EN in addition to the narrow minor groove of the T-tract, leading to the enhanced nicking efficiency observed at the junction.
true
true
true
true
true
219
1
DISCUSSION
1
19
[ "B19", "B42", "B42" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
On a strained substrate such as supercoiled plasmid DNA, the difference between cleaving T-tract DNA and a poly(T)-A junction would probably be even more pronounced.
[ "19", "42", "42" ]
165
1,256
0
false
On a strained substrate such as supercoiled plasmid DNA, the difference between cleaving T-tract DNA and a poly(T)-A junction would probably be even more pronounced.
[]
On a strained substrate such as supercoiled plasmid DNA, the difference between cleaving T-tract DNA and a poly(T)-A junction would probably be even more pronounced.
true
true
true
true
true
219
1
DISCUSSION
1
19
[ "B19", "B42", "B42" ]
17,626,046
NA|pmid-12411507|pmid-7679954|pmid-16490214|pmid-9922177|pmid-14739342|pmid-14739342
The torsional strain might widen the minor groove at the junction even further and facilitate the structural recognition of the DNA target.
[ "19", "42", "42" ]
139
1,257
0
false
The torsional strain might widen the minor groove at the junction even further and facilitate the structural recognition of the DNA target.
[]
The torsional strain might widen the minor groove at the junction even further and facilitate the structural recognition of the DNA target.
true
true
true
true
true
219
2
DISCUSSION
1
27
[ "B27" ]
17,626,046
pmid-16093679|pmid-10838565|pmid-15274918
Although the structure of L1-EN would allow the accommodation of a flipped nucleotide at position (+1) downstream of the scissile bond (27), we do not find any evidence for the base-specific recognition of such a nucleotide.
[ "27" ]
224
1,258
1
false
Although the structure of L1-EN would allow the accommodation of a flipped nucleotide at position (+1) downstream of the scissile bond, we do not find any evidence for the base-specific recognition of such a nucleotide.
[ "27" ]
Although the structure of L1-EN would allow the accommodation of a flipped nucleotide at position (+1) downstream of the scissile bond, we do not find any evidence for the base-specific recognition of such a nucleotide.
true
true
true
true
true
220
2
DISCUSSION
1
27
[ "B27" ]
17,626,046
pmid-16093679|pmid-10838565|pmid-15274918
At least for the initial target recognition the nucleotide needs to be part of a downstream stem.
[ "27" ]
97
1,259
0
false
At least for the initial target recognition the nucleotide needs to be part of a downstream stem.
[]
At least for the initial target recognition the nucleotide needs to be part of a downstream stem.
true
true
true
true
true
220
2
DISCUSSION
1
27
[ "B27" ]
17,626,046
pmid-16093679|pmid-10838565|pmid-15274918
However, this does not rule out the possibility that the flexibility (or ‘flippability’) of the nucleotide is required in consecutive steps of the integration process.
[ "27" ]
167
1,260
0
false
However, this does not rule out the possibility that the flexibility (or ‘flippability’) of the nucleotide is required in consecutive steps of the integration process.
[]
However, this does not rule out the possibility that the flexibility (or ‘flippability’) of the nucleotide is required in consecutive steps of the integration process.
true
true
true
true
true
220
3
DISCUSSION
1
9
[ "B9", "B43", "B8" ]
17,626,046
pmid-16093679|pmid-2447482|pmid-2550791|pmid-10648607|pmid-9482842|pmid-1662412|pmid-12176319|pmid-12176320|NA|pmid-9922177|pmid-8945517|pmid-16728505|pmid-16735504|pmid-16936727|pmid-9260521|pmid-16093679|pmid-12006980|pmid-16490214
In conclusion, L1-EN recognizes structural features of the DNA target rather than specific nucleotides in the sequence.
[ "9", "43", "8" ]
119
1,261
0
false
In conclusion, L1-EN recognizes structural features of the DNA target rather than specific nucleotides in the sequence.
[]
In conclusion, L1-EN recognizes structural features of the DNA target rather than specific nucleotides in the sequence.
true
true
true
true
true
221
3
DISCUSSION
1
9
[ "B9", "B43", "B8" ]
17,626,046
pmid-16093679|pmid-2447482|pmid-2550791|pmid-10648607|pmid-9482842|pmid-1662412|pmid-12176319|pmid-12176320|NA|pmid-9922177|pmid-8945517|pmid-16728505|pmid-16735504|pmid-16936727|pmid-9260521|pmid-16093679|pmid-12006980|pmid-16490214
The 5′ TTTT/AA 3′ integration site consensus sequence may fulfill these structural requirements in an ideal way, but many alternative sequences seem to have similar structural features and are nicked in vitro.
[ "9", "43", "8" ]
209
1,262
0
false
The 5′ TTTT/AA 3′ integration site consensus sequence may fulfill these structural requirements in an ideal way, but many alternative sequences seem to have similar structural features and are nicked in vitro.
[]
The 5′ TTTT/AA 3′ integration site consensus sequence may fulfill these structural requirements in an ideal way, but many alternative sequences seem to have similar structural features and are nicked in vitro.
true
true
true
true
true
221
3
DISCUSSION
1
9
[ "B9", "B43", "B8" ]
17,626,046
pmid-16093679|pmid-2447482|pmid-2550791|pmid-10648607|pmid-9482842|pmid-1662412|pmid-12176319|pmid-12176320|NA|pmid-9922177|pmid-8945517|pmid-16728505|pmid-16735504|pmid-16936727|pmid-9260521|pmid-16093679|pmid-12006980|pmid-16490214
The requirements for integration seem stricter than the requirements for nicking.
[ "9", "43", "8" ]
81
1,263
0
false
The requirements for integration seem stricter than the requirements for nicking.
[]
The requirements for integration seem stricter than the requirements for nicking.
true
true
true
true
true
221
3
DISCUSSION
1
9
[ "B9", "B43", "B8" ]
17,626,046
pmid-16093679|pmid-2447482|pmid-2550791|pmid-10648607|pmid-9482842|pmid-1662412|pmid-12176319|pmid-12176320|NA|pmid-9922177|pmid-8945517|pmid-16728505|pmid-16735504|pmid-16936727|pmid-9260521|pmid-16093679|pmid-12006980|pmid-16490214
This indicates that although the nicking specificity of the endonuclease is the primary determinant for integration site selection it may not be the only one (9).
[ "9", "43", "8" ]
162
1,264
1
false
This indicates that although the nicking specificity of the endonuclease is the primary determinant for integration site selection it may not be the only one.
[ "9" ]
This indicates that although the nicking specificity of the endonuclease is the primary determinant for integration site selection it may not be the only one.
true
true
true
true
true
221
3
DISCUSSION
1
9
[ "B9", "B43", "B8" ]
17,626,046
pmid-16093679|pmid-2447482|pmid-2550791|pmid-10648607|pmid-9482842|pmid-1662412|pmid-12176319|pmid-12176320|NA|pmid-9922177|pmid-8945517|pmid-16728505|pmid-16735504|pmid-16936727|pmid-9260521|pmid-16093679|pmid-12006980|pmid-16490214
Additional specificity factors could influence the choice of nicking site in the first place (co-targeting factors) or select among already nicked sites the ones that are suitable for integration (post-nicking factors).
[ "9", "43", "8" ]
219
1,265
0
false
Additional specificity factors could influence the choice of nicking site in the first place (co-targeting factors) or select among already nicked sites the ones that are suitable for integration (post-nicking factors).
[]
Additional specificity factors could influence the choice of nicking site in the first place (co-targeting factors) or select among already nicked sites the ones that are suitable for integration (post-nicking factors).
true
true
true
true
true
221
3
DISCUSSION
1
43
[ "B9", "B43", "B8" ]
17,626,046
pmid-16093679|pmid-2447482|pmid-2550791|pmid-10648607|pmid-9482842|pmid-1662412|pmid-12176319|pmid-12176320|NA|pmid-9922177|pmid-8945517|pmid-16728505|pmid-16735504|pmid-16936727|pmid-9260521|pmid-16093679|pmid-12006980|pmid-16490214
The latter possibility is favored by reports of endonuclease-independent retrotransposition (43) and L1-induced chromosomal breaks (8).
[ "9", "43", "8" ]
135
1,266
1
false
The latter possibility is favored by reports of endonuclease-independent retrotransposition and L1-induced chromosomal breaks.
[ "43", "8" ]
The latter possibility is favored by reports of endonuclease-independent retrotransposition and L1-induced chromosomal breaks.
true
true
true
true
true
221
4
DISCUSSION
1
41
[ "B41", "B14", "B27" ]
17,626,046
pmid-10648607|pmid-9482842|pmid-9922177|pmid-11823433|pmid-12644555|pmid-15247245|pmid-9482842|pmid-15274918
During DNA target site recognition, the conformational space available to the downstream DNA duplex is probed by the insertion of the βB6–βB5 beta-hairpin loop of L1-EN into the minor groove at a poly(T)-A junction, according to the presented model (Figure 3D).
[ "41", "14", "27" ]
261
1,267
0
false
During DNA target site recognition, the conformational space available to the downstream DNA duplex is probed by the insertion of the βB6–βB5 beta-hairpin loop of L1-EN into the minor groove at a poly(T)-A junction, according to the presented model (Figure 3D).
[]
During DNA target site recognition, the conformational space available to the downstream DNA duplex is probed by the insertion of the βB6–βB5 beta-hairpin loop of L1-EN into the minor groove at a poly(T)-A junction, according to the presented model (Figure 3D).
true
true
true
true
true
222
4
DISCUSSION
1
41
[ "B41", "B14", "B27" ]
17,626,046
pmid-10648607|pmid-9482842|pmid-9922177|pmid-11823433|pmid-12644555|pmid-15247245|pmid-9482842|pmid-15274918
The presence of the loop is important for nicking activity and both nicking activity and target specificity are very sensitive to structural changes of the loop, especially at its tip.
[ "41", "14", "27" ]
184
1,268
0
false
The presence of the loop is important for nicking activity and both nicking activity and target specificity are very sensitive to structural changes of the loop, especially at its tip.
[]
The presence of the loop is important for nicking activity and both nicking activity and target specificity are very sensitive to structural changes of the loop, especially at its tip.
true
true
true
true
true
222
4
DISCUSSION
1
41
[ "B41", "B14", "B27" ]
17,626,046
pmid-10648607|pmid-9482842|pmid-9922177|pmid-11823433|pmid-12644555|pmid-15247245|pmid-9482842|pmid-15274918
Similar to the situation in TRAS1-EN (41) a deletion of the tip (LR1) or of the entire loop (L3G) results in an altered specificity and much reduced activity.
[ "41", "14", "27" ]
158
1,269
1
false
Similar to the situation in TRAS1-EN a deletion of the tip (LR1) or of the entire loop (L3G) results in an altered specificity and much reduced activity.
[ "41" ]
Similar to the situation in TRAS1-EN a deletion of the tip or of the entire loop (L3G) results in an altered specificity and much reduced activity.
true
true
true
true
true
222
4
DISCUSSION
1
41
[ "B41", "B14", "B27" ]
17,626,046
pmid-10648607|pmid-9482842|pmid-9922177|pmid-11823433|pmid-12644555|pmid-15247245|pmid-9482842|pmid-15274918
To examine the importance of the amino acid sequence we exchanged residue H198 in the tip of the loop, which had no impact on the nicking pattern.
[ "41", "14", "27" ]
146
1,270
0
false
To examine the importance of the amino acid sequence we exchanged residue H198 in the tip of the loop, which had no impact on the nicking pattern.
[]
To examine the importance of the amino acid sequence we exchanged residue H198 in the tip of the loop, which had no impact on the nicking pattern.
true
true
true
true
true
222
4
DISCUSSION
1
41
[ "B41", "B14", "B27" ]
17,626,046
pmid-10648607|pmid-9482842|pmid-9922177|pmid-11823433|pmid-12644555|pmid-15247245|pmid-9482842|pmid-15274918
Even the substitution of the entire loop with a different sequence and an extended reverse turn (LTx) was tolerated rather well.
[ "41", "14", "27" ]
128
1,271
0
false
Even the substitution of the entire loop with a different sequence and an extended reverse turn (LTx) was tolerated rather well.
[]
Even the substitution of the entire loop with a different sequence and an extended reverse turn (LTx) was tolerated rather well.
true
true
true
true
true
222
4
DISCUSSION
1
41
[ "B41", "B14", "B27" ]
17,626,046
pmid-10648607|pmid-9482842|pmid-9922177|pmid-11823433|pmid-12644555|pmid-15247245|pmid-9482842|pmid-15274918
This suggests that the conformational flexibility of the beta-hairpin loop probing the DNA minor groove may be much more important than its sequence, especially if target recognition proceeds via the structural flexibility of the DNA at the poly(T)-A junction.
[ "41", "14", "27" ]
260
1,272
0
false
This suggests that the conformational flexibility of the beta-hairpin loop probing the DNA minor groove may be much more important than its sequence, especially if target recognition proceeds via the structural flexibility of the DNA at the poly(T)-A junction.
[]
This suggests that the conformational flexibility of the beta-hairpin loop probing the DNA minor groove may be much more important than its sequence, especially if target recognition proceeds via the structural flexibility of the DNA at the poly(T)-A junction.
true
true
true
true
true
222
4
DISCUSSION
1
41
[ "B41", "B14", "B27" ]
17,626,046
pmid-10648607|pmid-9482842|pmid-9922177|pmid-11823433|pmid-12644555|pmid-15247245|pmid-9482842|pmid-15274918
This hypothesis is supported by the presented Normal mode analysis.
[ "41", "14", "27" ]
67
1,273
0
false
This hypothesis is supported by the presented Normal mode analysis.
[]
This hypothesis is supported by the presented Normal mode analysis.
true
true
true
true
true
222
4
DISCUSSION
1
41
[ "B41", "B14", "B27" ]
17,626,046
pmid-10648607|pmid-9482842|pmid-9922177|pmid-11823433|pmid-12644555|pmid-15247245|pmid-9482842|pmid-15274918
The βB6–βB5 hairpin loop of LTx may be able to functionally replace the βB6–βB5 hairpin loop of L1-EN because it is flexible enough to insert partially into the minor groove of many L1-EN targets to probe the conformational space of the downstream duplex.
[ "41", "14", "27" ]
255
1,274
0
false
The βB6–βB5 hairpin loop of LTx may be able to functionally replace the βB6–βB5 hairpin loop of L1-EN because it is flexible enough to insert partially into the minor groove of many L1-EN targets to probe the conformational space of the downstream duplex.
[]
The βB6–βB5 hairpin loop of LTx may be able to functionally replace the βB6–βB5 hairpin loop of L1-EN because it is flexible enough to insert partially into the minor groove of many L1-EN targets to probe the conformational space of the downstream duplex.
true
true
true
true
true
222
4
DISCUSSION
1
41
[ "B41", "B14", "B27" ]
17,626,046
pmid-10648607|pmid-9482842|pmid-9922177|pmid-11823433|pmid-12644555|pmid-15247245|pmid-9482842|pmid-15274918
The βB6–βB5 hairpin loop of LR1 may be too rigid for this function.
[ "41", "14", "27" ]
67
1,275
0
false
The βB6–βB5 hairpin loop of LR1 may be too rigid for this function.
[]
The βB6–βB5 hairpin loop of LR1 may be too rigid for this function.
true
true
true
true
true
222
4
DISCUSSION
1
14
[ "B41", "B14", "B27" ]
17,626,046
pmid-10648607|pmid-9482842|pmid-9922177|pmid-11823433|pmid-12644555|pmid-15247245|pmid-9482842|pmid-15274918
In its natural context on R1Bm-EN (14) it may only be required as a counter bearing for the target DNA, which would then be probed sequence specifically from the side of the major groove by a unique extension of surface loop βB4–αB2, predicted for R1Bm-EN (27).
[ "41", "14", "27" ]
261
1,276
1
false
In its natural context on R1Bm-EN it may only be required as a counter bearing for the target DNA, which would then be probed sequence specifically from the side of the major groove by a unique extension of surface loop βB4–αB2, predicted for R1Bm-EN.
[ "14", "27" ]
In its natural context on R1Bm-EN it may only be required as a counter bearing for the target DNA, which would then be probed sequence specifically from the side of the major groove by a unique extension of surface loop βB4–αB2, predicted for R1Bm-EN.
true
true
true
true
true
222
5
DISCUSSION
1
44
[ "B44", "B45", "B46", "B9", "B27" ]
17,626,046
pmid-15274918|pmid-11700292|pmid-15578988|pmid-17124176|pmid-16093679|pmid-15274918
The L1 retrotransposon bears considerable potential as a genetic tool (44).
[ "44", "45", "46", "9", "27" ]
75
1,277
1
false
The L1 retrotransposon bears considerable potential as a genetic tool.
[ "44" ]
The L1 retrotransposon bears considerable potential as a genetic tool.
true
true
true
true
true
223
5
DISCUSSION
1
45
[ "B44", "B45", "B46", "B9", "B27" ]
17,626,046
pmid-15274918|pmid-11700292|pmid-15578988|pmid-17124176|pmid-16093679|pmid-15274918
It can be delivered to cells by an adenovirus vector (45) and its suitability for in vivo mutagenesis has recently been demonstrated with a synthetic, highly active mouse L1 element called ORFeus (46).
[ "44", "45", "46", "9", "27" ]
201
1,278
1
false
It can be delivered to cells by an adenovirus vector and its suitability for in vivo mutagenesis has recently been demonstrated with a synthetic, highly active mouse L1 element called ORFeus.
[ "45", "46" ]
It can be delivered to cells by an adenovirus vector and its suitability for in vivo mutagenesis has recently been demonstrated with a synthetic, highly active mouse L1 element called ORFeus.
true
true
true
true
true
223
5
DISCUSSION
1
44
[ "B44", "B45", "B46", "B9", "B27" ]
17,626,046
pmid-15274918|pmid-11700292|pmid-15578988|pmid-17124176|pmid-16093679|pmid-15274918
The application of similar L1 retrotransposons for gene delivery into defined genomic locations requires engineering of the endonuclease target specificity as one of the most crucial steps.
[ "44", "45", "46", "9", "27" ]
189
1,279
0
false
The application of similar L1 retrotransposons for gene delivery into defined genomic locations requires engineering of the endonuclease target specificity as one of the most crucial steps.
[]
The application of similar L1 retrotransposons for gene delivery into defined genomic locations requires engineering of the endonuclease target specificity as one of the most crucial steps.
true
true
true
true
true
223
5
DISCUSSION
1
44
[ "B44", "B45", "B46", "B9", "B27" ]
17,626,046
pmid-15274918|pmid-11700292|pmid-15578988|pmid-17124176|pmid-16093679|pmid-15274918
This appears feasible since there are many natural APE-type non-LTR retrotransposon endonucleases with distinct target specificities that all share the same protein scaffold and the same catalytic site (9,27).
[ "44", "45", "46", "9", "27" ]
209
1,280
0
false
This appears feasible since there are many natural APE-type non-LTR retrotransposon endonucleases with distinct target specificities that all share the same protein scaffold and the same catalytic site.
[ "9,27" ]
This appears feasible since there are many natural APE-type non-LTR retrotransposon endonucleases with distinct target specificities that all share the same protein scaffold and the same catalytic site.
true
true
true
true
true
223
6
DISCUSSION
1
47
[ "B47", "B48", "B49" ]
17,626,046
pmid-15568024|pmid-3713831|pmid-16439663
Loop grafting experiments have been shown to mimic evolutionary processes (47), allowing novel specificities to be engineered (48,49).
[ "47", "48", "49" ]
134
1,281
1
false
Loop grafting experiments have been shown to mimic evolutionary processes, allowing novel specificities to be engineered.
[ "47", "48,49" ]
Loop grafting experiments have been shown to mimic evolutionary processes, allowing novel specificities to be engineered.
true
true
true
true
true
224
6
DISCUSSION
1
47
[ "B47", "B48", "B49" ]
17,626,046
pmid-15568024|pmid-3713831|pmid-16439663
The analysis of the presented L1-EN βB6–βB5 hairpin loop variants shows that the respective grafting experiments worked successfully from a structural point of view and that other surface loops may be manipulated in a similar way in the future.
[ "47", "48", "49" ]
244
1,282
0
false
The analysis of the presented L1-EN βB6–βB5 hairpin loop variants shows that the respective grafting experiments worked successfully from a structural point of view and that other surface loops may be manipulated in a similar way in the future.
[]
The analysis of the presented L1-EN βB6–βB5 hairpin loop variants shows that the respective grafting experiments worked successfully from a structural point of view and that other surface loops may be manipulated in a similar way in the future.
true
true
true
true
true
224
6
DISCUSSION
1
47
[ "B47", "B48", "B49" ]
17,626,046
pmid-15568024|pmid-3713831|pmid-16439663
From a functional point of view, we could show that the DNA nicking profile of L1-EN is quite sensitive to structural changes of the studied loop and that novel specificities can indeed be acquired.
[ "47", "48", "49" ]
198
1,283
0
false
From a functional point of view, we could show that the DNA nicking profile of L1-EN is quite sensitive to structural changes of the studied loop and that novel specificities can indeed be acquired.
[]
From a functional point of view, we could show that the DNA nicking profile of L1-EN is quite sensitive to structural changes of the studied loop and that novel specificities can indeed be acquired.
true
true
true
true
true
224
6
DISCUSSION
1
47
[ "B47", "B48", "B49" ]
17,626,046
pmid-15568024|pmid-3713831|pmid-16439663
For further improvements high-resolution structures of retrotransposon endonucleases in complex with their respective DNA targets would be of great help.
[ "47", "48", "49" ]
153
1,284
0
false
For further improvements high-resolution structures of retrotransposon endonucleases in complex with their respective DNA targets would be of great help.
[]
For further improvements high-resolution structures of retrotransposon endonucleases in complex with their respective DNA targets would be of great help.
true
true
true
true
true
224
7
DISCUSSION
0
null
null
17,626,046
null
Finally, the apparent existence of additional targeting factors poses further challenges and opportunities for the engineering of novel integration specificities.
null
162
1,285
0
false
null
null
Finally, the apparent existence of additional targeting factors poses further challenges and opportunities for the engineering of novel integration specificities.
true
true
true
true
true
225
7
DISCUSSION
0
null
null
17,626,046
null
One such factor may be the contribution from complementary bases between the 3′ end of retrotransposon RNA and the 3′ end of nicked genomic DNA.
null
144
1,286
0
false
null
null
One such factor may be the contribution from complementary bases between the 3′ end of retrotransposon RNA and the 3′ end of nicked genomic DNA.
true
true
true
true
true
225
7
DISCUSSION
0
null
null
17,626,046
null
Tools like the LTx variant will allow us to investigate these effects in the future.
null
84
1,287
0
false
null
null
Tools like the LTx variant will allow us to investigate these effects in the future.
true
true
true
true
true
225
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
RNA interference (RNAi) has become an extremely useful genetic tool to study gene function in mammalian cells.
[ "1", "2", "3", "4", "5", "6", "7" ]
110
1,288
0
false
RNA interference (RNAi) has become an extremely useful genetic tool to study gene function in mammalian cells.
[]
RNA interference (RNAi) has become an extremely useful genetic tool to study gene function in mammalian cells.
true
true
true
true
true
226
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
The discovery that short double-stranded RNAs, known as short interfering (si)RNAs, avoid an interferon response and the global shutdown of translation has enabled the wide use of transient gene silencing in cultured cells and specific tissues of mice upon local administration (1).
[ "1", "2", "3", "4", "5", "6", "7" ]
282
1,289
1
false
The discovery that short double-stranded RNAs, known as short interfering (si)RNAs, avoid an interferon response and the global shutdown of translation has enabled the wide use of transient gene silencing in cultured cells and specific tissues of mice upon local administration.
[ "1" ]
The discovery that short double-stranded RNAs, known as short interfering (si)RNAs, avoid an interferon response and the global shutdown of translation has enabled the wide use of transient gene silencing in cultured cells and specific tissues of mice upon local administration.
true
true
true
true
true
226
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
To elicit permanent gene silencing, short hairpin (sh)RNA expression vectors can be used.
[ "1", "2", "3", "4", "5", "6", "7" ]
89
1,290
0
false
To elicit permanent gene silencing, short hairpin (sh)RNA expression vectors can be used.
[]
To elicit permanent gene silencing, short hairpin (sh)RNA expression vectors can be used.
true
true
true
true
true
226
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
These vectors consist of an RNA polymerase III promoter producing short RNA fragments, which form hairpin structures.
[ "1", "2", "3", "4", "5", "6", "7" ]
117
1,291
0
false
These vectors consist of an RNA polymerase III promoter producing short RNA fragments, which form hairpin structures.
[]
These vectors consist of an RNA polymerase III promoter producing short RNA fragments, which form hairpin structures.
true
true
true
true
true
226
0
INTRODUCTION
1
2
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
These shRNAs are processed by the RNAi machinery in the same way as linear double-stranded RNAs such that sequence-specific gene silencing occurs (2).
[ "1", "2", "3", "4", "5", "6", "7" ]
150
1,292
1
false
These shRNAs are processed by the RNAi machinery in the same way as linear double-stranded RNAs such that sequence-specific gene silencing occurs.
[ "2" ]
These shRNAs are processed by the RNAi machinery in the same way as linear double-stranded RNAs such that sequence-specific gene silencing occurs.
true
true
true
true
true
226
0
INTRODUCTION
1
3
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
Mice transgenic for shRNA vectors produce an all-over knockdown phenotype, similar to conventional knockout mice (3).
[ "1", "2", "3", "4", "5", "6", "7" ]
117
1,293
1
false
Mice transgenic for shRNA vectors produce an all-over knockdown phenotype, similar to conventional knockout mice.
[ "3" ]
Mice transgenic for shRNA vectors produce an all-over knockdown phenotype, similar to conventional knockout mice.
true
true
true
true
true
226
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
To overcome the embryonic lethality of many mutants and to investigate gene functions in specific tissues or in a time dependent manner, conditional vectors have to be used.
[ "1", "2", "3", "4", "5", "6", "7" ]
173
1,294
0
false
To overcome the embryonic lethality of many mutants and to investigate gene functions in specific tissues or in a time dependent manner, conditional vectors have to be used.
[]
To overcome the embryonic lethality of many mutants and to investigate gene functions in specific tissues or in a time dependent manner, conditional vectors have to be used.
true
true
true
true
true
226
0
INTRODUCTION
1
4
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
ShRNA expression can either be regulated by an inducing compound-like doxycycline acting on artificial regulatory sequences in the polymerase III promoter (4) or shRNA production is blocked by a transcriptional stop element that can be deleted through Cre mediated recombination.
[ "1", "2", "3", "4", "5", "6", "7" ]
279
1,295
1
false
ShRNA expression can either be regulated by an inducing compound-like doxycycline acting on artificial regulatory sequences in the polymerase III promoter or shRNA production is blocked by a transcriptional stop element that can be deleted through Cre mediated recombination.
[ "4" ]
ShRNA expression can either be regulated by an inducing compound-like doxycycline acting on artificial regulatory sequences in the polymerase III promoter or shRNA production is blocked by a transcriptional stop element that can be deleted through Cre mediated recombination.
true
true
true
true
true
226
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
The latter Cre/loxP approach is similar to conditional knockout or knock in strategies where it is widely used.
[ "1", "2", "3", "4", "5", "6", "7" ]
111
1,296
0
false
The latter Cre/loxP approach is similar to conditional knockout or knock in strategies where it is widely used.
[]
The latter Cre/loxP approach is similar to conditional knockout or knock in strategies where it is widely used.
true
true
true
true
true
226
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
Various vector designs for Cre/loxP regulated RNAi have been described (5,6).
[ "1", "2", "3", "4", "5", "6", "7" ]
77
1,297
0
false
Various vector designs for Cre/loxP regulated RNAi have been described.
[ "5,6" ]
Various vector designs for Cre/loxP regulated RNAi have been described.
true
true
true
true
true
226
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
Here, we show a fast and highly reproducible system to generate mice expressing shRNAs under the control of Cre recombinase.
[ "1", "2", "3", "4", "5", "6", "7" ]
124
1,298
0
false
Here, we show a fast and highly reproducible system to generate mice expressing shRNAs under the control of Cre recombinase.
[]
Here, we show a fast and highly reproducible system to generate mice expressing shRNAs under the control of Cre recombinase.
true
true
true
true
true
226
0
INTRODUCTION
1
7
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,586,814
pmid-13129706|pmid-12778125|pmid-12679785|pmid-12941798|pmid-15107481|pmid-15123829|pmid-11236674|pmid-11910072
This tool can be applied to a great variety of biological questions since a large collection of mouse strains that express Cre recombinase in specific cell types is available and can be used to activate conditional shRNA vectors at different developmental stages and in selected cell types of mice (7).
[ "1", "2", "3", "4", "5", "6", "7" ]
302
1,299
1
false
This tool can be applied to a great variety of biological questions since a large collection of mouse strains that express Cre recombinase in specific cell types is available and can be used to activate conditional shRNA vectors at different developmental stages and in selected cell types of mice.
[ "7" ]
This tool can be applied to a great variety of biological questions since a large collection of mouse strains that express Cre recombinase in specific cell types is available and can be used to activate conditional shRNA vectors at different developmental stages and in selected cell types of mice.
true
true
true
true
true
226