Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to
Stimulate Homologous Recombination

J 2015

Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination

TAYLOR, Martin R. G., Mário ŠPÍREK, Kathy R. CHAURASIYA, Jordan D. WARD, Raffaella CARZANIGA et. al.

Basic information

Original name

Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination

Authors

TAYLOR, Martin R. G. (826 United Kingdom of Great Britain and Northern Ireland), Mário ŠPÍREK (703 Slovakia, belonging to the institution), Kathy R. CHAURASIYA (826 United Kingdom of Great Britain and Northern Ireland), Jordan D. WARD (826 United Kingdom of Great Britain and Northern Ireland), Raffaella CARZANIGA (826 United Kingdom of Great Britain and Northern Ireland), Xiong YU (840 United States of America), Edward H. EGELMAN (840 United States of America), Lucy M. COLLINSON (826 United Kingdom of Great Britain and Northern Ireland), David RUEDA (826 United Kingdom of Great Britain and Northern Ireland), Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution) and Simon J. BOULTON (826 United Kingdom of Great Britain and Northern Ireland)

Edition

Cell, Cambridge, Cell Press, 2015, 0092-8674

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 28.710

RIV identification code

RIV/00216224:14110/15:00080948

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.cell.2015.06.015

UT WoS

000358087700009

Keywords in English

STRAND BREAK REPAIR; CANCER SUSCEPTIBILITY GENE; RECA PROTEIN; FANCONI-ANEMIA; DNA-DAMAGE; SACCHAROMYCES-CEREVISIAE; GERMLINE MUTATIONS; OVARIAN-CANCER; BRCA2; PROMOTES

Abstract

V originále

Repair of DNA double strand breaks by homologous recombination (HR) is initiated by Rad51 filament nucleation on single-stranded DNA (ssDNA), which catalyzes strand exchange with homologous duplex DNA. BRCA2 and the Rad51 paralogs are tumor suppressors and critical mediators of Rad51. To gain insight into Rad51 paralog function, we investigated a heterodimeric Rad51 paralog complex, RFS-1/RIP-1, and uncovered the molecular basis by which Rad51 paralogs promote HR. Unlike BRCA2, which nucleates RAD-51-ssDNA filaments, RFS-1/RIP-1 binds and remodels pre-synaptic filaments to a stabilized, "open,'' and flexible conformation, in which the ssDNA is more accessible to nuclease digestion and RAD-51 dissociation rate is reduced. Walker box mutations in RFS-1, which abolish filament remodeling, fail to stimulate RAD-51 strand exchange activity, demonstrating that remodeling is essential for RFS-1/RIP-1 function. We propose that Rad51 paralogs stimulate HR by remodeling the Rad51 filament, priming it for strand exchange with the template duplex.

Links

GAP207/12/2323, research and development project

Name: Endonuleazová a translokázová aktivita v restričních-modifikáčních komplexéch typu I

Investor: Czech Science Foundation

GA13-26629S, research and development project

Name: SUMO a stability genomu

Investor: Czech Science Foundation

Citovat

TAYLOR, Martin R. G., Mário ŠPÍREK, Kathy R. CHAURASIYA, Jordan D. WARD, Raffaella CARZANIGA, Xiong YU, Edward H. EGELMAN, Lucy M. COLLINSON, David RUEDA, Lumír KREJČÍ and Simon J. BOULTON. Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination. Cell. Cambridge: Cell Press, 2015, vol. 162, No 2, p. 271-286. ISSN 0092-8674. Available from: https://dx.doi.org/10.1016/j.cell.2015.06.015.

@article{1308439,
   author = {Taylor, Martin R. G. and Špírek, Mário and Chaurasiya, Kathy R. and Ward, Jordan D. and Carzaniga, Raffaella and Yu, Xiong and Egelman, Edward H. and Collinson, Lucy M. and Rueda, David and Krejčí, Lumír and Boulton, Simon J.},
   article_location = {Cambridge},
   article_number = {2},
   doi = {http://dx.doi.org/10.1016/j.cell.2015.06.015},
   keywords = {STRAND BREAK REPAIR; CANCER SUSCEPTIBILITY GENE; RECA PROTEIN; FANCONI-ANEMIA; DNA-DAMAGE; SACCHAROMYCES-CEREVISIAE; GERMLINE MUTATIONS; OVARIAN-CANCER; BRCA2; PROMOTES},
   language = {eng},
   issn = {0092-8674},
   journal = {Cell},
   title = {Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination},
   volume = {162},
   year = {2015}
}

TY  - JOUR
ID  - 1308439
AU  - Taylor, Martin R. G. - Špírek, Mário - Chaurasiya, Kathy R. - Ward, Jordan D. - Carzaniga, Raffaella - Yu, Xiong - Egelman, Edward H. - Collinson, Lucy M. - Rueda, David - Krejčí, Lumír - Boulton, Simon J.
PY  - 2015
TI  - Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination
JF  - Cell
VL  - 162
IS  - 2
SP  - 271-286
EP  - 271-286
PB  - Cell Press
SN  - 00928674
KW  - STRAND BREAK REPAIR
KW  - CANCER SUSCEPTIBILITY GENE
KW  - RECA PROTEIN
KW  - FANCONI-ANEMIA
KW  - DNA-DAMAGE
KW  - SACCHAROMYCES-CEREVISIAE
KW  - GERMLINE MUTATIONS
KW  - OVARIAN-CANCER
KW  - BRCA2
KW  - PROMOTES
N2  - Repair of DNA double strand breaks by homologous recombination (HR) is initiated by Rad51 filament nucleation on single-stranded DNA (ssDNA), which catalyzes strand exchange with homologous duplex DNA. BRCA2 and the Rad51 paralogs are tumor suppressors and critical mediators of Rad51. To gain insight into Rad51 paralog function, we investigated a heterodimeric Rad51 paralog complex, RFS-1/RIP-1, and uncovered the molecular basis by which Rad51 paralogs promote HR. Unlike BRCA2, which nucleates RAD-51-ssDNA filaments, RFS-1/RIP-1 binds and remodels pre-synaptic filaments to a stabilized, "open,'' and flexible conformation, in which the ssDNA is more accessible to nuclease digestion and RAD-51 dissociation rate is reduced. Walker box mutations in RFS-1, which abolish filament remodeling, fail to stimulate RAD-51 strand exchange activity, demonstrating that remodeling is essential for RFS-1/RIP-1 function. We propose that Rad51 paralogs stimulate HR by remodeling the Rad51 filament, priming it for strand exchange with the template duplex.
ER  -

TAYLOR, Martin R. G., Mário ŠPÍREK, Kathy R. CHAURASIYA, Jordan D. WARD, Raffaella CARZANIGA, Xiong YU, Edward H. EGELMAN, Lucy M. COLLINSON, David RUEDA, Lumír KREJČÍ and Simon J. BOULTON. Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination. \textit{Cell}. Cambridge: Cell Press, 2015, vol.~162, No~2, p.~271-286. ISSN~0092-8674. Available from: https://dx.doi.org/10.1016/j.cell.2015.06.015.

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