Datasets:
vgainullin
/
xciting_data

Dataset card Data Studio Files
xet
 Community
1
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4
INTRODUCTION
1
20
[ "B20", "B20", "B21" ]
17,264,124
pmid-12408862|pmid-12408862|pmid-15655113|pmid-15655113|pmid-10526232
The fusion of Spo11 protein to the Gal4 DNA-binding domain (Gal4BD-Spo11), as accomplished by us in a previous study, produced a novel experimental tool that enabled additional information about molecular mechanism of the DSB cleavage by Spo11 to be determined (20).
[ "20", "20", "21" ]
266
600
1
false
The fusion of Spo11 protein to the Gal4 DNA-binding domain (Gal4BD-Spo11), as accomplished by us in a previous study, produced a novel experimental tool that enabled additional information about molecular mechanism of the DSB cleavage by Spo11 to be determined.
[ "20" ]
The fusion of Spo11 protein to the Gal4 DNA-binding domain (Gal4BD-Spo11), as accomplished by us in a previous study, produced a novel experimental tool that enabled additional information about molecular mechanism of the DSB cleavage by Spo11 to be determined.
true
true
true
true
true
101
4
INTRODUCTION
1
20
[ "B20", "B20", "B21" ]
17,264,124
pmid-12408862|pmid-12408862|pmid-15655113|pmid-15655113|pmid-10526232
Expression of Gal4BD-Spo11 in spo11Δ diploids allowed recombinogenic DSB formation at innate DSB sites and wild-type production of viable spores.
[ "20", "20", "21" ]
145
601
0
false
Expression of Gal4BD-Spo11 in spo11Δ diploids allowed recombinogenic DSB formation at innate DSB sites and wild-type production of viable spores.
[]
Expression of Gal4BD-Spo11 in spo11Δ diploids allowed recombinogenic DSB formation at innate DSB sites and wild-type production of viable spores.
true
true
true
true
true
101
4
INTRODUCTION
1
20
[ "B20", "B20", "B21" ]
17,264,124
pmid-12408862|pmid-12408862|pmid-15655113|pmid-15655113|pmid-10526232
In addition, Gal4BD-Spo11 expression allowed the targeted stimulation of novel DSB sites, located in the vicinity of Gal4 consensus-binding sites (UAS), such as in the GAL2 locus located within a DSB-cold domain on chromosome XII (20).
[ "20", "20", "21" ]
235
602
1
false
In addition, Gal4BD-Spo11 expression allowed the targeted stimulation of novel DSB sites, located in the vicinity of Gal4 consensus-binding sites (UAS), such as in the GAL2 locus located within a DSB-cold domain on chromosome XII.
[ "20" ]
In addition, Gal4BD-Spo11 expression allowed the targeted stimulation of novel DSB sites, located in the vicinity of Gal4 consensus-binding sites (UAS), such as in the GAL2 locus located within a DSB-cold domain on chromosome XII.
true
true
true
true
true
101
4
INTRODUCTION
1
20
[ "B20", "B20", "B21" ]
17,264,124
pmid-12408862|pmid-12408862|pmid-15655113|pmid-15655113|pmid-10526232
In that study, we examined the genetic requirements for the formation of these targeted DSBs.
[ "20", "20", "21" ]
93
603
0
false
In that study, we examined the genetic requirements for the formation of these targeted DSBs.
[]
In that study, we examined the genetic requirements for the formation of these targeted DSBs.
true
true
true
true
true
101
4
INTRODUCTION
1
20
[ "B20", "B20", "B21" ]
17,264,124
pmid-12408862|pmid-12408862|pmid-15655113|pmid-15655113|pmid-10526232
Interestingly, we found that DSB formation at the targeted DSB sites required all of the known factors (DSB proteins and Clb5-Clb6) that are indispensable for DSB formation at innate DSB sites.
[ "20", "20", "21" ]
193
604
0
false
Interestingly, we found that DSB formation at the targeted DSB sites required all of the known factors (DSB proteins and Clb5-Clb6) that are indispensable for DSB formation at innate DSB sites.
[]
Interestingly, we found that DSB formation at the targeted DSB sites required all of the known factors (DSB proteins and Clb5-Clb6) that are indispensable for DSB formation at innate DSB sites.
true
true
true
true
true
101
4
INTRODUCTION
1
20
[ "B20", "B20", "B21" ]
17,264,124
pmid-12408862|pmid-12408862|pmid-15655113|pmid-15655113|pmid-10526232
This indicated that Gal4BD-Spo11 catalyzes DSB formation near the Gal4 UAS by locally recruiting the components necessary for DSB formation, whereas they might be absent or improperly localized in DSB-cold domains.
[ "20", "20", "21" ]
214
605
0
false
This indicated that Gal4BD-Spo11 catalyzes DSB formation near the Gal4 UAS by locally recruiting the components necessary for DSB formation, whereas they might be absent or improperly localized in DSB-cold domains.
[]
This indicated that Gal4BD-Spo11 catalyzes DSB formation near the Gal4 UAS by locally recruiting the components necessary for DSB formation, whereas they might be absent or improperly localized in DSB-cold domains.
true
true
true
true
true
101
4
INTRODUCTION
1
20
[ "B20", "B20", "B21" ]
17,264,124
pmid-12408862|pmid-12408862|pmid-15655113|pmid-15655113|pmid-10526232
In this model, the binding of Spo11 to DSB sites would be the first rate-limiting step for DSB formation.
[ "20", "20", "21" ]
105
606
0
false
In this model, the binding of Spo11 to DSB sites would be the first rate-limiting step for DSB formation.
[]
In this model, the binding of Spo11 to DSB sites would be the first rate-limiting step for DSB formation.
true
true
true
true
true
101
4
INTRODUCTION
1
21
[ "B20", "B20", "B21" ]
17,264,124
pmid-12408862|pmid-12408862|pmid-15655113|pmid-15655113|pmid-10526232
However, the observation that uncleaved DNA intermediates are bound by Spo11 suggests that the activation of Spo11 cleavage is controlled separately from its physical interaction with DSB sites (21).
[ "20", "20", "21" ]
199
607
1
false
However, the observation that uncleaved DNA intermediates are bound by Spo11 suggests that the activation of Spo11 cleavage is controlled separately from its physical interaction with DSB sites.
[ "21" ]
However, the observation that uncleaved DNA intermediates are bound by Spo11 suggests that the activation of Spo11 cleavage is controlled separately from its physical interaction with DSB sites.
true
true
true
true
true
101
4
INTRODUCTION
1
20
[ "B20", "B20", "B21" ]
17,264,124
pmid-12408862|pmid-12408862|pmid-15655113|pmid-15655113|pmid-10526232
Thus, activation of Spo11 cleavage activity is likely more complex than initially anticipated.
[ "20", "20", "21" ]
94
608
0
false
Thus, activation of Spo11 cleavage activity is likely more complex than initially anticipated.
[]
Thus, activation of Spo11 cleavage activity is likely more complex than initially anticipated.
true
true
true
true
true
101
5
INTRODUCTION
0
null
null
17,264,124
pmid-15655113
Here, to provide insights into the activation and catalytic processes controlling Spo11 activity, we examined the in vivo interaction between Spo11 and Gal4BD-Spo11 proteins carrying distinct tags, and assayed their chromatin-binding and DSB formation activity at innate (YCR048w) and targeted (GAL2) sites.
null
307
609
0
false
null
null
Here, to provide insights into the activation and catalytic processes controlling Spo11 activity, we examined the in vivo interaction between Spo11 and Gal4BD-Spo11 proteins carrying distinct tags, and assayed their chromatin-binding and DSB formation activity at innate (YCR048w) and targeted (GAL2) sites.
true
true
true
true
true
102
5
INTRODUCTION
0
null
null
17,264,124
pmid-15655113
We demonstrate that Rec102, Rec104 and Rec114 regulate meiotic association between Spo11 subunits on chromatin sites.
null
117
610
0
false
null
null
We demonstrate that Rec102, Rec104 and Rec114 regulate meiotic association between Spo11 subunits on chromatin sites.
true
true
true
true
true
102
5
INTRODUCTION
0
null
null
17,264,124
pmid-15655113
Such meiotic self-association of Spo11 may be important for the regulation of DNA cleavage activity.
null
100
611
0
false
null
null
Such meiotic self-association of Spo11 may be important for the regulation of DNA cleavage activity.
true
true
true
true
true
102
0
DISCUSSION
0
null
null
17,264,124
pmid-11529427
In the present study, we examined the in vivo interaction between Spo11 proteins carrying distinct tags, and assayed chromatin binding and DSB formation at innate (YCR048w) and targeted (GAL2) sites upon fusion of Spo11 to the Gal4 DNA-binding domain.
null
251
612
0
false
null
null
In the present study, we examined the in vivo interaction between Spo11 proteins carrying distinct tags, and assayed chromatin binding and DSB formation at innate (YCR048w) and targeted (GAL2) sites upon fusion of Spo11 to the Gal4 DNA-binding domain.
true
true
true
true
true
103
0
DISCUSSION
0
null
null
17,264,124
pmid-11529427
We established that: (1) At the time of DSB formation, but not at premeiotic stages, the Spo11-3FLAG and Gal4BD-Spo11 proteins can form a heterocomplex; (2) In the presence of the Gal4BD-Spo11 protein, Spo11-3FLAG meiotically interacts with the preloaded Gal4BD-Spo11 protein and bound to the chromatin of the GAL2 region; (3) This interaction depends on other DSB proteins, since it is reduced in all DSB protein mutants, but more severely in rec102Δ, rec104Δ and rec114Δ mutants; and (4) Spo11-3FLAG is recruited to the GAL2 region in the presence of the nuclease-deficient Gal4BD-spo11Y135F protein, but remains inactive for DSB as well as potential SSB cleavage activity.
null
675
613
0
false
null
null
We established that: (1) At the time of DSB formation, but not at premeiotic stages, the Spo11-3FLAG and Gal4BD-Spo11 proteins can form a heterocomplex; (2) In the presence of the Gal4BD-Spo11 protein, Spo11-3FLAG meiotically interacts with the preloaded Gal4BD-Spo11 protein and bound to the chromatin of the GAL2 region; (3) This interaction depends on other DSB proteins, since it is reduced in all DSB protein mutants, but more severely in rec102Δ, rec104Δ and rec114Δ mutants; and (4) Spo11-3FLAG is recruited to the GAL2 region in the presence of the nuclease-deficient Gal4BD-spo11Y135F protein, but remains inactive for DSB as well as potential SSB cleavage activity.
true
true
true
true
true
103
1
DISCUSSION
0
null
null
17,264,124
pmid-9121560|pmid-9039264|pmid-16107854|pmid-12596227|pmid-10545127|pmid-11809802
Our time-course analysis of the Spo11-FLAG and Gal4BD-Spo11 interaction in diploid cells expressing both proteins under the control of the ADH1 promoter (Figure 1C) shows that the Gal4BD-Spo11-mediated recruitment of Spo11-3FLAG is enhanced during the period of DSB formation, although both proteins are present at generally constant levels during premeiosis and meiosis.
null
371
614
0
false
null
null
Our time-course analysis of the Spo11-FLAG and Gal4BD-Spo11 interaction in diploid cells expressing both proteins under the control of the ADH1 promoter (Figure 1C) shows that the Gal4BD-Spo11-mediated recruitment of Spo11-3FLAG is enhanced during the period of DSB formation, although both proteins are present at generally constant levels during premeiosis and meiosis.
true
true
true
true
true
104
1
DISCUSSION
0
null
null
17,264,124
pmid-9121560|pmid-9039264|pmid-16107854|pmid-12596227|pmid-10545127|pmid-11809802
In addition, they are co-immunoprecipitated only in the meiotic cell extracts.
null
78
615
0
false
null
null
In addition, they are co-immunoprecipitated only in the meiotic cell extracts.
true
true
true
true
true
104
1
DISCUSSION
0
null
null
17,264,124
pmid-9121560|pmid-9039264|pmid-16107854|pmid-12596227|pmid-10545127|pmid-11809802
All these data demonstrate that the self-interaction of Spo11 is controlled in a meiosis-dependent manner.
null
106
616
0
false
null
null
All these data demonstrate that the self-interaction of Spo11 is controlled in a meiosis-dependent manner.
true
true
true
true
true
104
2
DISCUSSION
1
29–31
[ "B29 B30 B31" ]
17,264,124
pmid-11529427|pmid-14992724|pmid-14992724|pmid-14967146|pmid-16783010|pmid-10526232|pmid-9799249|pmid-9435246|pmid-14988732|pmid-11231124|pmid-11231124|pmid-16814718|pmid-16698922|pmid-11805049|pmid-12897161|pmid-15044957
Our analysis of mutants indicates that the self-association of Spo11 is genetically controlled by the activity of other known meiotic DSB proteins (Figures 1E and 3).
[ "29–31" ]
166
617
0
false
Our analysis of mutants indicates that the self-association of Spo11 is genetically controlled by the activity of other known meiotic DSB proteins (Figures 1E and 3).
[]
Our analysis of mutants indicates that the self-association of Spo11 is genetically controlled by the activity of other known meiotic DSB proteins.
true
true
true
true
true
105
2
DISCUSSION
1
29–31
[ "B29 B30 B31" ]
17,264,124
pmid-11529427|pmid-14992724|pmid-14992724|pmid-14967146|pmid-16783010|pmid-10526232|pmid-9799249|pmid-9435246|pmid-14988732|pmid-11231124|pmid-11231124|pmid-16814718|pmid-16698922|pmid-11805049|pmid-12897161|pmid-15044957
In cells lacking Rec102 and Rec104, which physically interact with each other and with Spo11, the meiotic self-interaction of Spo11 decreases dramatically (Figure 1E), suggesting that Rec102 and Rec104 may mediate the interaction between Spo11 subunits during meiosis via a physical interaction with Spo11 (Figure 7A) (29–31).
[ "29–31" ]
326
618
1
false
In cells lacking Rec102 and Rec104, which physically interact with each other and with Spo11, the meiotic self-interaction of Spo11 decreases dramatically (Figure 1E), suggesting that Rec102 and Rec104 may mediate the interaction between Spo11 subunits during meiosis via a physical interaction with Spo11 (Figure 7A).
[ "29–31" ]
In cells lacking Rec102 and Rec104, which physically interact with each other and with Spo11, the meiotic self-interaction of Spo11 decreases dramatically, suggesting that Rec102 and Rec104 may mediate the interaction between Spo11 subunits during meiosis via a physical interaction with Spo11 (Figure 7A).
true
true
true
true
true
105
2
DISCUSSION
1
29–31
[ "B29 B30 B31" ]
17,264,124
pmid-11529427|pmid-14992724|pmid-14992724|pmid-14967146|pmid-16783010|pmid-10526232|pmid-9799249|pmid-9435246|pmid-14988732|pmid-11231124|pmid-11231124|pmid-16814718|pmid-16698922|pmid-11805049|pmid-12897161|pmid-15044957
Figure 7.Schematic diagram of the complexes that are thought to assemble at the GAL2 UAS region at the time of meiotic DSB formation.
[ "29–31" ]
133
619
0
false
Figure 7.Schematic diagram of the complexes that are thought to assemble at the GAL2 UAS region at the time of meiotic DSB formation.
[]
Figure 7.Schematic diagram of the complexes that are thought to assemble at the GAL2 UAS region at the time of meiotic DSB formation.
true
true
true
true
true
105
2
DISCUSSION
1
29–31
[ "B29 B30 B31" ]
17,264,124
pmid-11529427|pmid-14992724|pmid-14992724|pmid-14967146|pmid-16783010|pmid-10526232|pmid-9799249|pmid-9435246|pmid-14988732|pmid-11231124|pmid-11231124|pmid-16814718|pmid-16698922|pmid-11805049|pmid-12897161|pmid-15044957
(A) Spo11 does not self-interact during premeiosis, but Spo11-3FLAG is meiotically recruited to the GAL2 UAS site, at which Gal4BD–Spo11 already exists, as shown in Figure 2D.
[ "29–31" ]
175
620
0
false
(A) Spo11 does not self-interact during premeiosis, but Spo11-3FLAG is meiotically recruited to the GAL2 UAS site, at which Gal4BD–Spo11 already exists, as shown in Figure 2D.
[]
(A) Spo11 does not self-interact during premeiosis, but Spo11-3FLAG is meiotically recruited to the GAL2 UAS site, at which Gal4BD–Spo11 already exists, as shown in Figure 2D.
false
false
true
true
false
105
2
DISCUSSION
1
29–31
[ "B29 B30 B31" ]
17,264,124
pmid-11529427|pmid-14992724|pmid-14992724|pmid-14967146|pmid-16783010|pmid-10526232|pmid-9799249|pmid-9435246|pmid-14988732|pmid-11231124|pmid-11231124|pmid-16814718|pmid-16698922|pmid-11805049|pmid-12897161|pmid-15044957
This association was not detected in rec102Δ, rec104Δ or rec114Δ cells by ChIP assay.
[ "29–31" ]
85
621
0
false
This association was not detected in rec102Δ, rec104Δ or rec114Δ cells by ChIP assay.
[]
This association was not detected in rec102Δ, rec104Δ or rec114Δ cells by ChIP assay.
true
true
true
true
true
105
2
DISCUSSION
1
29–31
[ "B29 B30 B31" ]
17,264,124
pmid-11529427|pmid-14992724|pmid-14992724|pmid-14967146|pmid-16783010|pmid-10526232|pmid-9799249|pmid-9435246|pmid-14988732|pmid-11231124|pmid-11231124|pmid-16814718|pmid-16698922|pmid-11805049|pmid-12897161|pmid-15044957
In the cells co-expressing Gal4BD-fused protein and Spo11-3FLAG, four types of Spo11 complex may assemble at the GAL2 UAS regions: homocomplexes consisting of either Gal4BD-fused protein alone or heterocomplexes consisting of both Gal4BD-fused protein and Spo11-3FLAG.
[ "29–31" ]
268
622
0
false
In the cells co-expressing Gal4BD-fused protein and Spo11-3FLAG, four types of Spo11 complex may assemble at the GAL2 UAS regions: homocomplexes consisting of either Gal4BD-fused protein alone or heterocomplexes consisting of both Gal4BD-fused protein and Spo11-3FLAG.
[]
In the cells co-expressing Gal4BD-fused protein and Spo11-3FLAG, four types of Spo11 complex may assemble at the GAL2 UAS regions: homocomplexes consisting of either Gal4BD-fused protein alone or heterocomplexes consisting of both Gal4BD-fused protein and Spo11-3FLAG.
true
true
true
true
true
105
2
DISCUSSION
1
29–31
[ "B29 B30 B31" ]
17,264,124
pmid-11529427|pmid-14992724|pmid-14992724|pmid-14967146|pmid-16783010|pmid-10526232|pmid-9799249|pmid-9435246|pmid-14988732|pmid-11231124|pmid-11231124|pmid-16814718|pmid-16698922|pmid-11805049|pmid-12897161|pmid-15044957
The homocomplexes of Gal4BD–spo11Y135F cannot introduce DSBs in the GAL2 UAS regions, but the heterocomplex of Gal4BD–spo11Y135F/Spo11-3FLAG is expected to catalyze DSB formation at least partly.
[ "29–31" ]
195
623
0
false
The homocomplexes of Gal4BD–spo11Y135F cannot introduce DSBs in the GAL2 UAS regions, but the heterocomplex of Gal4BD–spo11Y135F/Spo11-3FLAG is expected to catalyze DSB formation at least partly.
[]
The homocomplexes of Gal4BD–spo11Y135F cannot introduce DSBs in the GAL2 UAS regions, but the heterocomplex of Gal4BD–spo11Y135F/Spo11-3FLAG is expected to catalyze DSB formation at least partly.
true
true
true
true
true
105
2
DISCUSSION
1
29–31
[ "B29 B30 B31" ]
17,264,124
pmid-11529427|pmid-14992724|pmid-14992724|pmid-14967146|pmid-16783010|pmid-10526232|pmid-9799249|pmid-9435246|pmid-14988732|pmid-11231124|pmid-11231124|pmid-16814718|pmid-16698922|pmid-11805049|pmid-12897161|pmid-15044957
However, neither DSBs nor SSBs were detected in cells harboring such heterocomplexes (upper diagram).
[ "29–31" ]
101
624
0
false
However, neither DSBs nor SSBs were detected in cells harboring such heterocomplexes (upper diagram).
[]
However, neither DSBs nor SSBs were detected in cells harboring such heterocomplexes (upper diagram).
true
true
true
true
true
105
2
DISCUSSION
1
29–31
[ "B29 B30 B31" ]
17,264,124
pmid-11529427|pmid-14992724|pmid-14992724|pmid-14967146|pmid-16783010|pmid-10526232|pmid-9799249|pmid-9435246|pmid-14988732|pmid-11231124|pmid-11231124|pmid-16814718|pmid-16698922|pmid-11805049|pmid-12897161|pmid-15044957
In cells expressing both Gal4BD–Spo11 and spo11Y135F-3FLAG, the heterocomplex of Gal4BD–Spo11/spo11Y135F-3FLAG formed in the GAL2 UAS regions is inactive (lower diagram).
[ "29–31" ]
170
625
0
false
In cells expressing both Gal4BD–Spo11 and spo11Y135F-3FLAG, the heterocomplex of Gal4BD–Spo11/spo11Y135F-3FLAG formed in the GAL2 UAS regions is inactive (lower diagram).
[]
In cells expressing both Gal4BD–Spo11 and spo11Y135F-3FLAG, the heterocomplex of Gal4BD–Spo11/spo11Y135F-3FLAG formed in the GAL2 UAS regions is inactive (lower diagram).
true
true
true
true
true
105
3
DISCUSSION
0
null
null
17,264,124
pmid-14967146|pmid-9144217|pmid-11027339
Schematic diagram of the complexes that are thought to assemble at the GAL2 UAS region at the time of meiotic DSB formation.
null
124
626
0
false
null
null
Schematic diagram of the complexes that are thought to assemble at the GAL2 UAS region at the time of meiotic DSB formation.
true
true
true
true
true
106
3
DISCUSSION
0
null
null
17,264,124
pmid-14967146|pmid-9144217|pmid-11027339
(A) Spo11 does not self-interact during premeiosis, but Spo11-3FLAG is meiotically recruited to the GAL2 UAS site, at which Gal4BD–Spo11 already exists, as shown in Figure 2D.
null
175
627
0
false
null
null
(A) Spo11 does not self-interact during premeiosis, but Spo11-3FLAG is meiotically recruited to the GAL2 UAS site, at which Gal4BD–Spo11 already exists, as shown in Figure 2D.
false
false
true
true
false
106
3
DISCUSSION
0
null
null
17,264,124
pmid-14967146|pmid-9144217|pmid-11027339
This association was not detected in rec102Δ, rec104Δ or rec114Δ cells by ChIP assay.
null
85
628
0
false
null
null
This association was not detected in rec102Δ, rec104Δ or rec114Δ cells by ChIP assay.
true
true
true
true
true
106
3
DISCUSSION
0
null
null
17,264,124
pmid-14967146|pmid-9144217|pmid-11027339
In the cells co-expressing Gal4BD-fused protein and Spo11-3FLAG, four types of Spo11 complex may assemble at the GAL2 UAS regions: homocomplexes consisting of either Gal4BD-fused protein alone or heterocomplexes consisting of both Gal4BD-fused protein and Spo11-3FLAG.
null
268
629
0
false
null
null
In the cells co-expressing Gal4BD-fused protein and Spo11-3FLAG, four types of Spo11 complex may assemble at the GAL2 UAS regions: homocomplexes consisting of either Gal4BD-fused protein alone or heterocomplexes consisting of both Gal4BD-fused protein and Spo11-3FLAG.
true
true
true
true
true
106
3
DISCUSSION
0
null
null
17,264,124
pmid-14967146|pmid-9144217|pmid-11027339
The homocomplexes of Gal4BD–spo11Y135F cannot introduce DSBs in the GAL2 UAS regions, but the heterocomplex of Gal4BD–spo11Y135F/Spo11-3FLAG is expected to catalyze DSB formation at least partly.
null
195
630
0
false
null
null
The homocomplexes of Gal4BD–spo11Y135F cannot introduce DSBs in the GAL2 UAS regions, but the heterocomplex of Gal4BD–spo11Y135F/Spo11-3FLAG is expected to catalyze DSB formation at least partly.
true
true
true
true
true
106
3
DISCUSSION
0
null
null
17,264,124
pmid-14967146|pmid-9144217|pmid-11027339
However, neither DSBs nor SSBs were detected in cells harboring such heterocomplexes (upper diagram).
null
101
631
0
false
null
null
However, neither DSBs nor SSBs were detected in cells harboring such heterocomplexes (upper diagram).
true
true
true
true
true
106
3
DISCUSSION
0
null
null
17,264,124
pmid-14967146|pmid-9144217|pmid-11027339
In cells expressing both Gal4BD–Spo11 and spo11Y135F-3FLAG, the heterocomplex of Gal4BD–Spo11/spo11Y135F-3FLAG formed in the GAL2 UAS regions is inactive (lower diagram).
null
170
632
0
false
null
null
In cells expressing both Gal4BD–Spo11 and spo11Y135F-3FLAG, the heterocomplex of Gal4BD–Spo11/spo11Y135F-3FLAG formed in the GAL2 UAS regions is inactive (lower diagram).
true
true
true
true
true
106
4
DISCUSSION
1
21
[ "B21", "B11" ]
17,264,124
pmid-12408862|pmid-12408862|pmid-15655113|pmid-15655113|pmid-10526232
Interestingly, the genetic requirements for the self-interaction of Spo11 as determined by the IP and ChIP experiments are somewhat different: Rec102 and Rec104 were absolutely required for the Spo11 self-interaction in the cell extracts, whereas Rec114 in addition to Rec102 and Rec104 was essential for the Gal4BD-Spo11-mediated recruitment of Spo11-3FLAG to the chromatin at the GAL2 UAS site (Figures 4 and 5).
[ "21", "11" ]
414
633
0
false
Interestingly, the genetic requirements for the self-interaction of Spo11 as determined by the IP and ChIP experiments are somewhat different: Rec102 and Rec104 were absolutely required for the Spo11 self-interaction in the cell extracts, whereas Rec114 in addition to Rec102 and Rec104 was essential for the Gal4BD-Spo11-mediated recruitment of Spo11-3FLAG to the chromatin at the GAL2 UAS site (Figures 4 and 5).
[]
Interestingly, the genetic requirements for the self-interaction of Spo11 as determined by the IP and ChIP experiments are somewhat different: Rec102 and Rec104 were absolutely required for the Spo11 self-interaction in the cell extracts, whereas Rec114 in addition to Rec102 and Rec104 was essential for the Gal4BD-Spo11-mediated recruitment of Spo11-3FLAG to the chromatin at the GAL2 UAS site (Figures 4 and 5).
true
true
true
true
true
107
4
DISCUSSION
1
21
[ "B21", "B11" ]
17,264,124
pmid-12408862|pmid-12408862|pmid-15655113|pmid-15655113|pmid-10526232
It is most likely that Rec114 is not involved in the Spo11 self-interaction, but has other roles in facilitating the initial chromatin binding of Spo11 (Figure 7A).
[ "21", "11" ]
164
634
0
false
It is most likely that Rec114 is not involved in the Spo11 self-interaction, but has other roles in facilitating the initial chromatin binding of Spo11 (Figure 7A).
[]
It is most likely that Rec114 is not involved in the Spo11 self-interaction, but has other roles in facilitating the initial chromatin binding of Spo11 (Figure 7A).
true
true
true
true
true
107
4
DISCUSSION
1
21
[ "B21", "B11" ]
17,264,124
pmid-12408862|pmid-12408862|pmid-15655113|pmid-15655113|pmid-10526232
This idea is consistent with the previous finding that the chromatin binding of Spo11 to DSB sites is not observed in rec114Δ strains (21).
[ "21", "11" ]
139
635
1
false
This idea is consistent with the previous finding that the chromatin binding of Spo11 to DSB sites is not observed in rec114Δ strains.
[ "21" ]
This idea is consistent with the previous finding that the chromatin binding of Spo11 to DSB sites is not observed in rec114Δ strains.
true
true
true
true
true
107
4
DISCUSSION
1
11
[ "B21", "B11" ]
17,264,124
pmid-12408862|pmid-12408862|pmid-15655113|pmid-15655113|pmid-10526232
In addition, the idea seems reasonable, since overproduction of Rec114 perturbs global DSB formation, presumably by an abortive chromatin loading of Spo11 proteins in the presence of an excess amount of Rec114 (11).
[ "21", "11" ]
215
636
1
false
In addition, the idea seems reasonable, since overproduction of Rec114 perturbs global DSB formation, presumably by an abortive chromatin loading of Spo11 proteins in the presence of an excess amount of Rec114.
[ "11" ]
In addition, the idea seems reasonable, since overproduction of Rec114 perturbs global DSB formation, presumably by an abortive chromatin loading of Spo11 proteins in the presence of an excess amount of Rec114.
true
true
true
true
true
107
5
DISCUSSION
1
21
[ "B21" ]
17,264,124
pmid-15655113
We also found that other meiotic DSB proteins, Mei4, Mer2 and Ski8, are partially required for Spo11-3FLAG recruitment to the GAL2 UAS site, although they are dispensable for the Spo11 self-interaction in meiotic cell extracts.
[ "21" ]
227
637
0
false
We also found that other meiotic DSB proteins, Mei4, Mer2 and Ski8, are partially required for Spo11-3FLAG recruitment to the GAL2 UAS site, although they are dispensable for the Spo11 self-interaction in meiotic cell extracts.
[]
We also found that other meiotic DSB proteins, Mei4, Mer2 and Ski8, are partially required for Spo11-3FLAG recruitment to the GAL2 UAS site, although they are dispensable for the Spo11 self-interaction in meiotic cell extracts.
true
true
true
true
true
108
5
DISCUSSION
1
21
[ "B21" ]
17,264,124
pmid-15655113
However, mei4Δ, mer2Δ and rec114Δ mutants had higher levels of Spo11 self-interaction (Figure 1E).
[ "21" ]
98
638
0
false
However, mei4Δ, mer2Δ and rec114Δ mutants had higher levels of Spo11 self-interaction (Figure 1E).
[]
However, mei4Δ, mer2Δ and rec114Δ mutants had higher levels of Spo11 self-interaction.
true
true
true
true
true
108
5
DISCUSSION
1
21
[ "B21" ]
17,264,124
pmid-15655113
Prieler et al.
[ "21" ]
14
639
0
false
Prieler et al.
[]
Prieler et al.
true
true
true
true
true
108
5
DISCUSSION
1
21
[ "B21" ]
17,264,124
pmid-15655113
have shown that Spo11-Myc forms aggregates in spread nuclei of rec114Δ mutants in addition to normal Spo11 foci, whereas no Spo11-Myc foci are detected at all in rec102Δ mutants (21).
[ "21" ]
183
640
1
false
have shown that Spo11-Myc forms aggregates in spread nuclei of rec114Δ mutants in addition to normal Spo11 foci, whereas no Spo11-Myc foci are detected at all in rec102Δ mutants.
[ "21" ]
have shown that Spo11-Myc forms aggregates in spread nuclei of rec114Δ mutants in addition to normal Spo11 foci, whereas no Spo11-Myc foci are detected at all in rec102Δ mutants.
false
true
true
true
false
108
5
DISCUSSION
1
21
[ "B21" ]
17,264,124
pmid-15655113
Thus, it is likely that polycomplex aggregates of Spo11 are formed in these three mutants.
[ "21" ]
90
641
0
false
Thus, it is likely that polycomplex aggregates of Spo11 are formed in these three mutants.
[]
Thus, it is likely that polycomplex aggregates of Spo11 are formed in these three mutants.
true
true
true
true
true
108
6
DISCUSSION
1
8
[ "B8" ]
17,264,124
pmid-14992724
It should be noted that Ski8 is known to interact with Spo11, and assists in the nuclear import of Spo11 during meiosis (8).
[ "8" ]
124
642
1
false
It should be noted that Ski8 is known to interact with Spo11, and assists in the nuclear import of Spo11 during meiosis.
[ "8" ]
It should be noted that Ski8 is known to interact with Spo11, and assists in the nuclear import of Spo11 during meiosis.
true
true
true
true
true
109
6
DISCUSSION
1
8
[ "B8" ]
17,264,124
pmid-14992724
Presumably Ski8 is not involved in controlling the Spo11 self-interaction, but has other roles as a direct partner of Spo11, for example acting to carry Spo11 into meiotic nuclei, converting Spo11 to a nuclease-active state, or stabilizing the binding of pre-DSB complexes to DSB sites.
[ "8" ]
286
643
0
false
Presumably Ski8 is not involved in controlling the Spo11 self-interaction, but has other roles as a direct partner of Spo11, for example acting to carry Spo11 into meiotic nuclei, converting Spo11 to a nuclease-active state, or stabilizing the binding of pre-DSB complexes to DSB sites.
[]
Presumably Ski8 is not involved in controlling the Spo11 self-interaction, but has other roles as a direct partner of Spo11, for example acting to carry Spo11 into meiotic nuclei, converting Spo11 to a nuclease-active state, or stabilizing the binding of pre-DSB complexes to DSB sites.
true
true
true
true
true
109
7
DISCUSSION
1
37
[ "B37" ]
17,264,124
pmid-1557122
We found that the Gal4BD-spo11Y135F-assisted recruitment of the functional Spo11-FLAG subunit to the GAL2 region is not active with respect to DSB or SSB activity.
[ "37" ]
163
644
0
false
We found that the Gal4BD-spo11Y135F-assisted recruitment of the functional Spo11-FLAG subunit to the GAL2 region is not active with respect to DSB or SSB activity.
[]
We found that the Gal4BD-spo11Y135F-assisted recruitment of the functional Spo11-FLAG subunit to the GAL2 region is not active with respect to DSB or SSB activity.
true
true
true
true
true
110
7
DISCUSSION
1
37
[ "B37" ]
17,264,124
pmid-1557122
This may be most simply explained by an excess occupancy of Gal4BD-spo11Y135F at GAL2 UAS site over the binding of Spo11-FLAG.
[ "37" ]
126
645
0
false
This may be most simply explained by an excess occupancy of Gal4BD-spo11Y135F at GAL2 UAS site over the binding of Spo11-FLAG.
[]
This may be most simply explained by an excess occupancy of Gal4BD-spo11Y135F at GAL2 UAS site over the binding of Spo11-FLAG.
true
true
true
true
true
110
7
DISCUSSION
1
37
[ "B37" ]
17,264,124
pmid-1557122
However, we think this may not be the case for the following reason.
[ "37" ]
68
646
0
false
However, we think this may not be the case for the following reason.
[]
However, we think this may not be the case for the following reason.
true
true
true
true
true
110
7
DISCUSSION
1
37
[ "B37" ]
17,264,124
pmid-1557122
Dimerization of Gal4BD-fused Spo11 may be facilitated via the dimerization between Gal4BD (37).
[ "37" ]
95
647
1
false
Dimerization of Gal4BD-fused Spo11 may be facilitated via the dimerization between Gal4BD.
[ "37" ]
Dimerization of Gal4BD-fused Spo11 may be facilitated via the dimerization between Gal4BD.
true
true
true
true
true
110
7
DISCUSSION
1
37
[ "B37" ]
17,264,124
pmid-1557122
Therefore, it is very likely that a homo-dimer Gal4BD-spo11Y135F preoccupies at the GAL2 UAS site.
[ "37" ]
98
648
0
false
Therefore, it is very likely that a homo-dimer Gal4BD-spo11Y135F preoccupies at the GAL2 UAS site.
[]
Therefore, it is very likely that a homo-dimer Gal4BD-spo11Y135F preoccupies at the GAL2 UAS site.
true
true
true
true
true
110
7
DISCUSSION
1
37
[ "B37" ]
17,264,124
pmid-1557122
The molecular ratio of Gal4BD-spo11Y135F versus Spo11-3FLAG at GAL2 UAS site is expected to be 1:0.6 (see above).
[ "37" ]
113
649
0
false
The molecular ratio of Gal4BD-spo11Y135F versus Spo11-3FLAG at GAL2 UAS site is expected to be 1:0.6 (see above).
[]
The molecular ratio of Gal4BD-spo11Y135F versus Spo11-3FLAG at GAL2 UAS site is expected to be 1:0.6 (see above).
true
true
true
true
true
110
7
DISCUSSION
1
37
[ "B37" ]
17,264,124
pmid-1557122
These results suggest that on average at least one wild-type Spo11 molecule is present at GAL2 UAS region forming a heterocomplex with Gal4BD-spo11Y135F, but cannot catalyze DNA cleavage reaction.
[ "37" ]
196
650
0
false
These results suggest that on average at least one wild-type Spo11 molecule is present at GAL2 UAS region forming a heterocomplex with Gal4BD-spo11Y135F, but cannot catalyze DNA cleavage reaction.
[]
These results suggest that on average at least one wild-type Spo11 molecule is present at GAL2 UAS region forming a heterocomplex with Gal4BD-spo11Y135F, but cannot catalyze DNA cleavage reaction.
true
true
true
true
true
110
7
DISCUSSION
1
37
[ "B37" ]
17,264,124
pmid-1557122
Therefore, it is suggested that multimeric assembly of active Spo11 monomers at DSB sites may be critical in DNA cleavage reaction.
[ "37" ]
131
651
0
false
Therefore, it is suggested that multimeric assembly of active Spo11 monomers at DSB sites may be critical in DNA cleavage reaction.
[]
Therefore, it is suggested that multimeric assembly of active Spo11 monomers at DSB sites may be critical in DNA cleavage reaction.
true
true
true
true
true
110
8
DISCUSSION
0
null
null
17,264,124
null
In this notion, one can predict that co-expression of Gal4BD-Spo11 and spo11 Y135F may exhibit a dominant negative effect on DSB formation at GAL2 UAS region.
null
158
652
0
false
null
null
In this notion, one can predict that co-expression of Gal4BD-Spo11 and spo11 Y135F may exhibit a dominant negative effect on DSB formation at GAL2 UAS region.
true
true
true
true
true
111
8
DISCUSSION
0
null
null
17,264,124
null
In fact, we observed 30–40% reduction of DSB formation at GAL2 UAS region in this situation (Figure 5C and D).
null
110
653
0
false
null
null
In fact, we observed 30–40% reduction of DSB formation at GAL2 UAS region in this situation (Figure 5C and D).
true
true
true
true
true
111
8
DISCUSSION
0
null
null
17,264,124
null
The partial (but not total) reduction of DSB formation at GAL2 UAS region can be explained as follows.
null
102
654
0
false
null
null
The partial (but not total) reduction of DSB formation at GAL2 UAS region can be explained as follows.
true
true
true
true
true
111
8
DISCUSSION
0
null
null
17,264,124
null
At GAL2 UAS region in meiotic cells co-expressing Gal4BD–Spo11 and Spo11Y135F, there should be four types of Spo11 complexes (illustrated in Figure 7B, upper panel).
null
165
655
0
false
null
null
At GAL2 UAS region in meiotic cells co-expressing Gal4BD–Spo11 and Spo11Y135F, there should be four types of Spo11 complexes (illustrated in Figure 7B, upper panel).
true
true
true
true
true
111
8
DISCUSSION
0
null
null
17,264,124
null
Spo11-3FLAG homocomplex is present in nuclei, but cannot bind to GAL2 UAS regions without guidance by Gal4BD-spo11Y135F.
null
120
656
0
false
null
null
Spo11-3FLAG homocomplex is present in nuclei, but cannot bind to GAL2 UAS regions without guidance by Gal4BD-spo11Y135F.
true
true
true
true
true
111
8
DISCUSSION
0
null
null
17,264,124
null
Therefore, the GAL2 UAS is likely to be bound either by homocomplexes consisting of only Gal4BD-spo11Y135F, or by heterocomplexes consisting of Gal4BD-spo11Y135F and Spo11-3FLAG, which are all supposed to be inactive in the hypothesis.
null
235
657
0
false
null
null
Therefore, the GAL2 UAS is likely to be bound either by homocomplexes consisting of only Gal4BD-spo11Y135F, or by heterocomplexes consisting of Gal4BD-spo11Y135F and Spo11-3FLAG, which are all supposed to be inactive in the hypothesis.
true
true
true
true
true
111
8
DISCUSSION
0
null
null
17,264,124
null
The lower diagram of Figure 7B illustrates four potential situations at GAL2 UAS region in cells co-expressing Gal4BD-Spo11 and spo11Y135F.
null
139
658
0
false
null
null
The lower diagram of Figure 7B illustrates four potential situations at GAL2 UAS region in cells co-expressing Gal4BD-Spo11 and spo11Y135F.
true
true
true
true
true
111
8
DISCUSSION
0
null
null
17,264,124
null
In this case, three types (one type is half active) out of four possible combinations are assumed to catalyze DSB formation, thereby dominant negative effects may be only partial.
null
179
659
0
false
null
null
In this case, three types (one type is half active) out of four possible combinations are assumed to catalyze DSB formation, thereby dominant negative effects may be only partial.
true
true
true
true
true
111
9
DISCUSSION
1
5
[ "B5", "B6", "B6", "B7" ]
17,264,124
pmid-12596227|pmid-10545127|pmid-10545127|pmid-11809802
Since purification of active Spo11 proteins has not yet been achieved, it is difficult to estimate the exact number of Spo11 subunits present in an individual complex.
[ "5", "6", "6", "7" ]
167
660
0
false
Since purification of active Spo11 proteins has not yet been achieved, it is difficult to estimate the exact number of Spo11 subunits present in an individual complex.
[]
Since purification of active Spo11 proteins has not yet been achieved, it is difficult to estimate the exact number of Spo11 subunits present in an individual complex.
true
true
true
true
true
112
9
DISCUSSION
1
5
[ "B5", "B6", "B6", "B7" ]
17,264,124
pmid-12596227|pmid-10545127|pmid-10545127|pmid-11809802
However, biochemical and structural analyses of the archaeal Top6A protein complex suggest the participation of an anti-parallel dimer of Spo11 subunits in DSB cleavage (5,6).
[ "5", "6", "6", "7" ]
175
661
0
false
However, biochemical and structural analyses of the archaeal Top6A protein complex suggest the participation of an anti-parallel dimer of Spo11 subunits in DSB cleavage.
[ "5,6" ]
However, biochemical and structural analyses of the archaeal Top6A protein complex suggest the participation of an anti-parallel dimer of Spo11 subunits in DSB cleavage.
true
true
true
true
true
112
9
DISCUSSION
1
6
[ "B5", "B6", "B6", "B7" ]
17,264,124
pmid-12596227|pmid-10545127|pmid-10545127|pmid-11809802
In this idea, the location of the catalytic site of each protomer is closer to the magnesium-binding pocket in the Toprim domain of the other protomer than it is to its own (6).
[ "5", "6", "6", "7" ]
177
662
1
false
In this idea, the location of the catalytic site of each protomer is closer to the magnesium-binding pocket in the Toprim domain of the other protomer than it is to its own.
[ "6" ]
In this idea, the location of the catalytic site of each protomer is closer to the magnesium-binding pocket in the Toprim domain of the other protomer than it is to its own.
true
true
true
true
true
112
9
DISCUSSION
1
7
[ "B5", "B6", "B6", "B7" ]
17,264,124
pmid-12596227|pmid-10545127|pmid-10545127|pmid-11809802
The notion of anti-parallel interaction between Spo11 subunits is consistent with the partial dominant negative defects of DSB formation in heterozygous combinations of some DSB-defective alleles and Spo11-3HA (7).
[ "5", "6", "6", "7" ]
214
663
1
false
The notion of anti-parallel interaction between Spo11 subunits is consistent with the partial dominant negative defects of DSB formation in heterozygous combinations of some DSB-defective alleles and Spo11-3HA.
[ "7" ]
The notion of anti-parallel interaction between Spo11 subunits is consistent with the partial dominant negative defects of DSB formation in heterozygous combinations of some DSB-defective alleles and Spo11-3HA.
true
true
true
true
true
112
10
DISCUSSION
1
38
[ "B38", "B39" ]
17,264,124
pmid-9685374|pmid-9927662
In vitro biochemical analysis of yeast topoisomerase II has revealed that the catalytic tyrosine residue of one protomer causes SSBs in association with the metal-binding pocket of the other protomer (38,39).
[ "38", "39" ]
208
664
0
false
In vitro biochemical analysis of yeast topoisomerase II has revealed that the catalytic tyrosine residue of one protomer causes SSBs in association with the metal-binding pocket of the other protomer.
[ "38,39" ]
In vitro biochemical analysis of yeast topoisomerase II has revealed that the catalytic tyrosine residue of one protomer causes SSBs in association with the metal-binding pocket of the other protomer.
true
true
true
true
true
113
10
DISCUSSION
1
38
[ "B38", "B39" ]
17,264,124
pmid-9685374|pmid-9927662
Therefore, if Spo11 forms a dimer that functions via a topoisomerase-II-like mechanism, the heterocomplex of Gal4BD-spo11Y135F and Spo11-3FLAG should introduce an SSB at the GAL2 UAS.
[ "38", "39" ]
183
665
0
false
Therefore, if Spo11 forms a dimer that functions via a topoisomerase-II-like mechanism, the heterocomplex of Gal4BD-spo11Y135F and Spo11-3FLAG should introduce an SSB at the GAL2 UAS.
[]
Therefore, if Spo11 forms a dimer that functions via a topoisomerase-II-like mechanism, the heterocomplex of Gal4BD-spo11Y135F and Spo11-3FLAG should introduce an SSB at the GAL2 UAS.
true
true
true
true
true
113
10
DISCUSSION
1
38
[ "B38", "B39" ]
17,264,124
pmid-9685374|pmid-9927662
However, this is not the case (Figure 6).
[ "38", "39" ]
41
666
0
false
However, this is not the case (Figure 6).
[]
However, this is not the case (Figure 6).
true
true
true
true
true
113
10
DISCUSSION
1
38
[ "B38", "B39" ]
17,264,124
pmid-9685374|pmid-9927662
It seems likely that the mechanism by which Spo11 cleaves DNA is slightly different from the way that topoisomerase II functions.
[ "38", "39" ]
129
667
0
false
It seems likely that the mechanism by which Spo11 cleaves DNA is slightly different from the way that topoisomerase II functions.
[]
It seems likely that the mechanism by which Spo11 cleaves DNA is slightly different from the way that topoisomerase II functions.
true
true
true
true
true
113
10
DISCUSSION
1
38
[ "B38", "B39" ]
17,264,124
pmid-9685374|pmid-9927662
Presumably, two active catalytic tyrosine residues in a dimeric configuration are essential to function in concert to generate DSBs.
[ "38", "39" ]
132
668
0
false
Presumably, two active catalytic tyrosine residues in a dimeric configuration are essential to function in concert to generate DSBs.
[]
Presumably, two active catalytic tyrosine residues in a dimeric configuration are essential to function in concert to generate DSBs.
true
true
true
true
true
113
11
DISCUSSION
0
null
null
17,264,124
null
In cells co-expressing Gal4BD-spo11Y135F and Spo11-3FLAG, we detected only faint levels of DSB formation at the UAS within the YCR048w coding region, suggesting that DSB formation is impaired, but not absent at this locus, whereas no DSB was detected at the GAL2 UAS site.
null
272
669
0
false
null
null
In cells co-expressing Gal4BD-spo11Y135F and Spo11-3FLAG, we detected only faint levels of DSB formation at the UAS within the YCR048w coding region, suggesting that DSB formation is impaired, but not absent at this locus, whereas no DSB was detected at the GAL2 UAS site.
true
true
true
true
true
114
11
DISCUSSION
0
null
null
17,264,124
null
The former locus is in a chromosomal domain that is very active in meiotic DSB formation, but the latter site is in a DSB-cold domain.
null
134
670
0
false
null
null
The former locus is in a chromosomal domain that is very active in meiotic DSB formation, but the latter site is in a DSB-cold domain.
true
true
true
true
true
114
11
DISCUSSION
0
null
null
17,264,124
null
Differences in the effects on DSB formation at the two UAS-containing sites may reflect regional conditions that limit or favor DSB formation.
null
142
671
0
false
null
null
Differences in the effects on DSB formation at the two UAS-containing sites may reflect regional conditions that limit or favor DSB formation.
true
true
true
true
true
114
11
DISCUSSION
0
null
null
17,264,124
null
In DSB-cold domains, it is possible that Spo11 and its activating factors may be absent or present only in small amounts, so that DSB formation is more severely affected in comparison with the situation at DSB-hot domains, at which Spo11 and its activating factors may be more readily available.
null
295
672
0
false
null
null
In DSB-cold domains, it is possible that Spo11 and its activating factors may be absent or present only in small amounts, so that DSB formation is more severely affected in comparison with the situation at DSB-hot domains, at which Spo11 and its activating factors may be more readily available.
true
true
true
true
true
114
11
DISCUSSION
0
null
null
17,264,124
null
In fact, the molecular ratios of Gal4BD-Spo11 (or Gal4BD-spo11Y135F) versus Spo11-3FLAG at GAL2 UAS and YCR048w regions are 1:0.6 and 1:5.8, respectively.
null
154
673
0
false
null
null
In fact, the molecular ratios of Gal4BD-Spo11 (or Gal4BD-spo11Y135F) versus Spo11-3FLAG at GAL2 UAS and YCR048w regions are 1:0.6 and 1:5.8, respectively.
true
true
true
true
true
114
11
DISCUSSION
0
null
null
17,264,124
null
Therefore, Spo11 may be able to form larger multimers in DSB-hot domains than in DSB-cold domains.
null
98
674
0
false
null
null
Therefore, Spo11 may be able to form larger multimers in DSB-hot domains than in DSB-cold domains.
true
true
true
true
true
114
11
DISCUSSION
0
null
null
17,264,124
null
In such larger Spo11 multimers, a small portion of active complexes can exist and sufficiently catalyze DSB formation; thereby the presence of Gal4BD-spo11Y135F hardly interferes with the DSB activity of active Spo11 proteins at innate DSB sites in DSB-hot domains.
null
265
675
0
false
null
null
In such larger Spo11 multimers, a small portion of active complexes can exist and sufficiently catalyze DSB formation; thereby the presence of Gal4BD-spo11Y135F hardly interferes with the DSB activity of active Spo11 proteins at innate DSB sites in DSB-hot domains.
true
true
true
true
true
114
11
DISCUSSION
0
null
null
17,264,124
null
It will be interesting to test the possibility of regional regulation of DSB formation in terms of the interaction between Spo11 subunits.
null
138
676
0
false
null
null
It will be interesting to test the possibility of regional regulation of DSB formation in terms of the interaction between Spo11 subunits.
true
true
true
true
true
114
12
DISCUSSION
1
21
[ "B21", "B9" ]
17,264,124
pmid-15655113|pmid-14967146
Activation of Spo11 is controlled separately from the control of its physical interaction with DSB sites, since there are uncleaved DNA intermediates bound by Spo11, without introducing any nicks (21).
[ "21", "9" ]
201
677
1
false
Activation of Spo11 is controlled separately from the control of its physical interaction with DSB sites, since there are uncleaved DNA intermediates bound by Spo11, without introducing any nicks.
[ "21" ]
Activation of Spo11 is controlled separately from the control of its physical interaction with DSB sites, since there are uncleaved DNA intermediates bound by Spo11, without introducing any nicks.
true
true
true
true
true
115
12
DISCUSSION
1
9
[ "B21", "B9" ]
17,264,124
pmid-15655113|pmid-14967146
We also found that Spo11 can bind to DSB-cold regions such as centromeric regions (K. Kugou et al., unpublished results), and that Gal4BD-Spo11 binds to GAL2 UAS sites without cleaving DNA (9).
[ "21", "9" ]
193
678
1
false
We also found that Spo11 can bind to DSB-cold regions such as centromeric regions (K. Kugou et al., unpublished results), and that Gal4BD-Spo11 binds to GAL2 UAS sites without cleaving DNA.
[ "9" ]
We also found that Spo11 can bind to DSB-cold regions such as centromeric regions (K. Kugou et al., unpublished results), and that Gal4BD-Spo11 binds to GAL2 UAS sites without cleaving DNA.
true
true
true
true
true
115
12
DISCUSSION
1
21
[ "B21", "B9" ]
17,264,124
pmid-15655113|pmid-14967146
It is therefore possible that Spo11 complexes at DSB-cold regions do not participate in the DNA cleavage reaction unless they are converted to active complexes with the assistance of other DSB factors.
[ "21", "9" ]
201
679
0
false
It is therefore possible that Spo11 complexes at DSB-cold regions do not participate in the DNA cleavage reaction unless they are converted to active complexes with the assistance of other DSB factors.
[]
It is therefore possible that Spo11 complexes at DSB-cold regions do not participate in the DNA cleavage reaction unless they are converted to active complexes with the assistance of other DSB factors.
true
true
true
true
true
115
12
DISCUSSION
1
21
[ "B21", "B9" ]
17,264,124
pmid-15655113|pmid-14967146
Since Rec102 and Rec104 are involved in the meiotic self-interaction of Spo11, these meiotic DSB factors are assumed to play important roles in the regulation of Spo11 activity by controlling the self-interaction between Spo11 monomers, thereby facilitating the formation of the pre-DSB complex.
[ "21", "9" ]
295
680
0
false
Since Rec102 and Rec104 are involved in the meiotic self-interaction of Spo11, these meiotic DSB factors are assumed to play important roles in the regulation of Spo11 activity by controlling the self-interaction between Spo11 monomers, thereby facilitating the formation of the pre-DSB complex.
[]
Since Rec102 and Rec104 are involved in the meiotic self-interaction of Spo11, these meiotic DSB factors are assumed to play important roles in the regulation of Spo11 activity by controlling the self-interaction between Spo11 monomers, thereby facilitating the formation of the pre-DSB complex.
true
true
true
true
true
115
13
DISCUSSION
0
null
null
17,264,124
null
The present analyses reveal that Spo11 molecules can interact with each other, and are genetically controlled by meiotic DSB proteins such as Rec102, Rec104 and Rec114.
null
168
681
0
false
null
null
The present analyses reveal that Spo11 molecules can interact with each other, and are genetically controlled by meiotic DSB proteins such as Rec102, Rec104 and Rec114.
true
true
true
true
true
116
13
DISCUSSION
0
null
null
17,264,124
null
This finding permits new insights into the molecular mechanisms of DSB cleavage and regulation of cleavage activity by Spo11.
null
125
682
0
false
null
null
This finding permits new insights into the molecular mechanisms of DSB cleavage and regulation of cleavage activity by Spo11.
true
true
true
true
true
116
0
INTRODUCTION
1
1
[ "B1", "B2", "B3 B4 B5 B6" ]
17,584,792
NA|NA|pmid-12613654|NA|pmid-16967918|NA|pmid-17233600|NA
A serious limitation of the use of many types of synthetic oligonucleotides (ON) and their analogues as therapeutic antisense agents has been their poor cellular delivery (1,2).
[ "1", "2", "3–6" ]
177
683
0
false
A serious limitation of the use of many types of synthetic oligonucleotides (ON) and their analogues as therapeutic antisense agents has been their poor cellular delivery.
[ "1,2" ]
A serious limitation of the use of many types of synthetic oligonucleotides (ON) and their analogues as therapeutic antisense agents has been their poor cellular delivery.
true
true
true
true
true
117
0
INTRODUCTION
1
1
[ "B1", "B2", "B3 B4 B5 B6" ]
17,584,792
NA|NA|pmid-12613654|NA|pmid-16967918|NA|pmid-17233600|NA
Many types of vector have been designed to aid ON delivery both for cell culture and in vivo.
[ "1", "2", "3–6" ]
93
684
0
false
Many types of vector have been designed to aid ON delivery both for cell culture and in vivo.
[]
Many types of vector have been designed to aid ON delivery both for cell culture and in vivo.
true
true
true
true
true
117
0
INTRODUCTION
1
3–6
[ "B1", "B2", "B3 B4 B5 B6" ]
17,584,792
NA|NA|pmid-12613654|NA|pmid-16967918|NA|pmid-17233600|NA
Amongst such strategies, conjugation to cell penetrating peptides (CPP) has received much recent attention (3–6).
[ "1", "2", "3–6" ]
113
685
1
false
Amongst such strategies, conjugation to cell penetrating peptides (CPP) has received much recent attention.
[ "3–6" ]
Amongst such strategies, conjugation to cell penetrating peptides (CPP) has received much recent attention.
true
true
true
true
true
117
1
INTRODUCTION
1
7
[ "B7", "B8", "B9", "B10" ]
17,584,792
pmid-10807948|NA|pmid-15640444|pmid-17113327|pmid-9572837|NA
In the case of negatively charged antisense ON, the potential of conjugated CPPs for delivery has not been realized, since there are very few publications that have shown significant biological activity (7,8).
[ "7", "8", "9", "10" ]
209
686
0
false
In the case of negatively charged antisense ON, the potential of conjugated CPPs for delivery has not been realized, since there are very few publications that have shown significant biological activity.
[ "7,8" ]
In the case of negatively charged antisense ON, the potential of conjugated CPPs for delivery has not been realized, since there are very few publications that have shown significant biological activity.
true
true
true
true
true
118
1
INTRODUCTION
1
9
[ "B7", "B8", "B9", "B10" ]
17,584,792
pmid-10807948|NA|pmid-15640444|pmid-17113327|pmid-9572837|NA
Indeed, a recent study with a well-controlled assay dealing with inhibition of trans-activation of the HIV-1 LTR showed some significant cell internalization of a number of CPP-ONs, but a complete lack of biological activity (9).
[ "7", "8", "9", "10" ]
229
687
1
false
Indeed, a recent study with a well-controlled assay dealing with inhibition of trans-activation of the HIV-1 LTR showed some significant cell internalization of a number of CPP-ONs, but a complete lack of biological activity.
[ "9" ]
Indeed, a recent study with a well-controlled assay dealing with inhibition of trans-activation of the HIV-1 LTR showed some significant cell internalization of a number of CPP-ONs, but a complete lack of biological activity.
true
true
true
true
true
118
1
INTRODUCTION
1
10
[ "B7", "B8", "B9", "B10" ]
17,584,792
pmid-10807948|NA|pmid-15640444|pmid-17113327|pmid-9572837|NA
In addition, only very modest biological activity was found for similar CPPs conjugated to synthetic short interference RNA (siRNA) targeted to a P38 MAP kinase mRNA (10).
[ "7", "8", "9", "10" ]
171
688
1
false
In addition, only very modest biological activity was found for similar CPPs conjugated to synthetic short interference RNA (siRNA) targeted to a P38 MAP kinase mRNA.
[ "10" ]
In addition, only very modest biological activity was found for similar CPPs conjugated to synthetic short interference RNA (siRNA) targeted to a P38 MAP kinase mRNA.
true
true
true
true
true
118
2
INTRODUCTION
1
11
[ "B11", "B12 B13 B14 B15 B16 B17 B18 B19" ]
17,584,792
pmid-9572837|pmid-11574678|NA|pmid-15148357|pmid-16220989|pmid-16610796|NA|NA|pmid-17233600|NA
A particularly useful HeLa cell assay for assessing the activity of CPP-ONs conjugates in a comparative manner is that established by Kole and colleagues (11) involving splice correction of an aberrant β-globin intron by 16-mer synthetic oligonucleotides (705 site) and subsequent up-regulation of firefly luciferase.
[ "11", "12–19" ]
317
689
1
false
A particularly useful HeLa cell assay for assessing the activity of CPP-ONs conjugates in a comparative manner is that established by Kole and colleagues involving splice correction of an aberrant β-globin intron by 16-mer synthetic oligonucleotides (705 site) and subsequent up-regulation of firefly luciferase.
[ "11" ]
A particularly useful HeLa cell assay for assessing the activity of CPP-ONs conjugates in a comparative manner is that established by Kole and colleagues involving splice correction of an aberrant β-globin intron by 16-mer synthetic oligonucleotides (705 site) and subsequent up-regulation of firefly luciferase.
true
true
true
true
true
119
2
INTRODUCTION
1
11
[ "B11", "B12 B13 B14 B15 B16 B17 B18 B19" ]
17,584,792
pmid-9572837|pmid-11574678|NA|pmid-15148357|pmid-16220989|pmid-16610796|NA|NA|pmid-17233600|NA
This assay is straightforward to carry out and has a very high dynamic range, such that even very low activity levels can be seen as a positive luminescence read-out.
[ "11", "12–19" ]
166
690
0
false
This assay is straightforward to carry out and has a very high dynamic range, such that even very low activity levels can be seen as a positive luminescence read-out.
[]
This assay is straightforward to carry out and has a very high dynamic range, such that even very low activity levels can be seen as a positive luminescence read-out.
true
true
true
true
true
119
2
INTRODUCTION
1
11
[ "B11", "B12 B13 B14 B15 B16 B17 B18 B19" ]
17,584,792
pmid-9572837|pmid-11574678|NA|pmid-15148357|pmid-16220989|pmid-16610796|NA|NA|pmid-17233600|NA
CPPs conjugated to ONs that are not negatively charged, such as peptide nucleic acids (PNA) or phosphoramidate morpholino oligonucleotides (PMO) have shown significant promise in splicing correction assays and other steric block applications, for which PNA is particularly suited.
[ "11", "12–19" ]
280
691
0
false
CPPs conjugated to ONs that are not negatively charged, such as peptide nucleic acids (PNA) or phosphoramidate morpholino oligonucleotides (PMO) have shown significant promise in splicing correction assays and other steric block applications, for which PNA is particularly suited.
[]
CPPs conjugated to ONs that are not negatively charged, such as peptide nucleic acids (PNA) or phosphoramidate morpholino oligonucleotides (PMO) have shown significant promise in splicing correction assays and other steric block applications, for which PNA is particularly suited.
true
true
true
true
true
119
2
INTRODUCTION
1
12–19
[ "B11", "B12 B13 B14 B15 B16 B17 B18 B19" ]
17,584,792
pmid-9572837|pmid-11574678|NA|pmid-15148357|pmid-16220989|pmid-16610796|NA|NA|pmid-17233600|NA
For many PNA conjugates, biological activity in this and other splice alteration assays has been observed when the PNA is attached to cationic, amphipathic or other CPP peptides, but concentrations of conjugates in the 5–10 µM range almost invariably have been needed for incubation with cultured cells to see significant splice alteration activity (12–19).
[ "11", "12–19" ]
357
692
1
false
For many PNA conjugates, biological activity in this and other splice alteration assays has been observed when the PNA is attached to cationic, amphipathic or other CPP peptides, but concentrations of conjugates in the 5–10 µM range almost invariably have been needed for incubation with cultured cells to see significant splice alteration activity.
[ "12–19" ]
For many PNA conjugates, biological activity in this and other splice alteration assays has been observed when the PNA is attached to cationic, amphipathic or other CPP peptides, but concentrations of conjugates in the 5–10 µM range almost invariably have been needed for incubation with cultured cells to see significant splice alteration activity.
true
true
true
true
true
119
3
INTRODUCTION
1
19–23
[ "B19 B20 B21 B22 B23", "B24", "B25", "B20", "B21", "B26", "B17 B18 B19", "B23", "B27", "B19", "B18" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
Recent studies by our laboratories (19–23) and by other groups (24,25) have demonstrated that a major barrier for nuclear delivery, required for splicing correction, is the release from endocytic vesicular compartments.
[ "19–23", "24", "25", "20", "21", "26", "17–19", "23", "27", "19", "18" ]
219
693
1
false
Recent studies by our laboratories and by other groups have demonstrated that a major barrier for nuclear delivery, required for splicing correction, is the release from endocytic vesicular compartments.
[ "19–23", "24,25" ]
Recent studies by our laboratories and by other groups have demonstrated that a major barrier for nuclear delivery, required for splicing correction, is the release from endocytic vesicular compartments.
true
true
true
true
true
120
3
INTRODUCTION
1
20
[ "B19 B20 B21 B22 B23", "B24", "B25", "B20", "B21", "B26", "B17 B18 B19", "B23", "B27", "B19", "B18" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
This was not surprising since, for polycationic CPPs such as Tat, Penetratin, R9 or K8, the vast majority of the material is internalized by an active mechanism of endocytosis, which involves electrostatic interactions with cellular heparan sulphates, and has little access to the nuclear compartment (20).
[ "19–23", "24", "25", "20", "21", "26", "17–19", "23", "27", "19", "18" ]
306
694
1
false
This was not surprising since, for polycationic CPPs such as Tat, Penetratin, R9 or K8, the vast majority of the material is internalized by an active mechanism of endocytosis, which involves electrostatic interactions with cellular heparan sulphates, and has little access to the nuclear compartment.
[ "20" ]
This was not surprising since, for polycationic CPPs such as Tat, Penetratin, R9 or K8, the vast majority of the material is internalized by an active mechanism of endocytosis, which involves electrostatic interactions with cellular heparan sulphates, and has little access to the nuclear compartment.
true
true
true
true
true
120
3
INTRODUCTION
1
19–23
[ "B19 B20 B21 B22 B23", "B24", "B25", "B20", "B21", "B26", "B17 B18 B19", "B23", "B27", "B19", "B18" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
Endosomolytic agents, such as chloroquine, calcium ions or high sucrose concentration (21,26), are necessary to obtain a significant splice correction activity (17–19,23), but the use of such agents in vivo is difficult to envisage.
[ "19–23", "24", "25", "20", "21", "26", "17–19", "23", "27", "19", "18" ]
232
695
0
false
Endosomolytic agents, such as chloroquine, calcium ions or high sucrose concentration, are necessary to obtain a significant splice correction activity, but the use of such agents in vivo is difficult to envisage.
[ "21,26", "17–19,23" ]
Endosomolytic agents, such as chloroquine, calcium ions or high sucrose concentration, are necessary to obtain a significant splice correction activity, but the use of such agents in vivo is difficult to envisage.
true
true
true
true
true
120
3
INTRODUCTION
1
19–23
[ "B19 B20 B21 B22 B23", "B24", "B25", "B20", "B21", "B26", "B17 B18 B19", "B23", "B27", "B19", "B18" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
One possible solution is to complement the CPP with a membrane-destabilizing agent (e.g.
[ "19–23", "24", "25", "20", "21", "26", "17–19", "23", "27", "19", "18" ]
88
696
0
false
One possible solution is to complement the CPP with a membrane-destabilizing agent (e.g.
[]
One possible solution is to complement the CPP with a membrane-destabilizing agent (e.g.
true
true
true
true
true
120
3
INTRODUCTION
1
27
[ "B19 B20 B21 B22 B23", "B24", "B25", "B20", "B21", "B26", "B17 B18 B19", "B23", "B27", "B19", "B18" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
viral fusogenic peptide or membrane-destabilizing peptide), such as has been proposed by Dowdy to improve CPP-mediated protein transfection (27), or to screen for a new peptide additive that might improve the biological activity of the CPP conjugate.
[ "19–23", "24", "25", "20", "21", "26", "17–19", "23", "27", "19", "18" ]
250
697
1
false
viral fusogenic peptide or membrane-destabilizing peptide), such as has been proposed by Dowdy to improve CPP-mediated protein transfection, or to screen for a new peptide additive that might improve the biological activity of the CPP conjugate.
[ "27" ]
viral fusogenic peptide or membrane-destabilizing peptide), such as has been proposed by Dowdy to improve CPP-mediated protein transfection, or to screen for a new peptide additive that might improve the biological activity of the CPP conjugate.
false
true
true
true
false
120
3
INTRODUCTION
1
19
[ "B19 B20 B21 B22 B23", "B24", "B25", "B20", "B21", "B26", "B17 B18 B19", "B23", "B27", "B19", "B18" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
In addition to the increased complexity of such a delivery system and to its cost, we have not been able to find to date a peptide or lipopeptide that showed substantially enhanced steric-block biological activity for a PNA ON conjugated to the Tat peptide (19).
[ "19–23", "24", "25", "20", "21", "26", "17–19", "23", "27", "19", "18" ]
262
698
1
false
In addition to the increased complexity of such a delivery system and to its cost, we have not been able to find to date a peptide or lipopeptide that showed substantially enhanced steric-block biological activity for a PNA ON conjugated to the Tat peptide.
[ "19" ]
In addition to the increased complexity of such a delivery system and to its cost, we have not been able to find to date a peptide or lipopeptide that showed substantially enhanced steric-block biological activity for a PNA ON conjugated to the Tat peptide.
true
true
true
true
true
120
3
INTRODUCTION
1
18
[ "B19 B20 B21 B22 B23", "B24", "B25", "B20", "B21", "B26", "B17 B18 B19", "B23", "B27", "B19", "B18" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
Likewise the co-incubation of 5 μM HA2–Penetratin fusion peptide with various CPP–PNA constructions had only a moderate effect on splice correction (18).
[ "19–23", "24", "25", "20", "21", "26", "17–19", "23", "27", "19", "18" ]
153
699
1
false
Likewise the co-incubation of 5 μM HA2–Penetratin fusion peptide with various CPP–PNA constructions had only a moderate effect on splice correction.
[ "18" ]
Likewise the co-incubation of 5 μM HA2–Penetratin fusion peptide with various CPP–PNA constructions had only a moderate effect on splice correction.
true
true
true
true
true
120