scholarly journals Mechanism of Replication Fork Reversal and Protection by Human RAD51 and RAD51 Paralogs

2020 ◽  
Author(s):  
Swagata Halder ◽  
Aurore Sanchez ◽  
Lepakshi Ranjha ◽  
Angelo Taglialatela ◽  
Giordano Reginato ◽  
...  
Keyword(s):  
Replication Fork ◽  
Rad51 Paralogs ◽  
Human Rad51

p53 Inhibits Strand Exchange and Replication Fork Regression Promoted by Human Rad51

2004 ◽  
Vol 336 (3) ◽  
pp. 639-654 ◽  
Author(s):  
Dennis Yoon ◽  
Yuzhen Wang ◽  
Kenneth Stapleford ◽  
Lisa Wiesmüller ◽  
Junghuei Chen
Keyword(s):  
Replication Fork ◽  
Strand Exchange ◽  
Fork Regression ◽  
Human Rad51

scholarly journals Non-enzymatic roles of human RAD51 at stalled replication forks

2018 ◽  
Author(s):  
Jennifer M. Mason ◽  
Yuen-Ling Chan ◽  
Ralph W. Weichselbaum ◽  
Douglas K. Bishop
Keyword(s):  
Dna Binding ◽  
Replication Fork ◽  
Replication Stress ◽  
Strand Exchange ◽  
Replication Forks ◽  
Enzymatic Function ◽  
Replication Restart ◽  
Stalled Replication Forks ◽  
Exchange Activity ◽  
Human Rad51

ABSTRACTThe central recombination enzyme RAD51 has been implicated in replication fork processing and restart in response to replication stress. Here, we use a separation-of-function allele of RAD51 that retains DNA binding, but not strand exchange activity, to reveal mechanistic aspects of RAD51’s roles in the response to replication stress. We find that cells lacking RAD51 strand exchange activity protect replication forks from MRE11-dependent degradation, as expected from previous studies. Unexpectedly we find that RAD51’s strand exchange activity is not required to convert stalled forks to a form that can be degraded by DNA2. Such conversion was shown previously to require replication fork reversal, supporting a model in which fork reversal depends on a non-enzymatic function of RAD51. We also show RAD51 promotes replication restart by both strand exchange-dependent and strand exchange-independent mechanisms.

scholarly journals RAD-ical New Insights into RAD51 Regulation

Genes ◽  
2018 ◽  
Vol 9 (12) ◽  
pp. 629 ◽  
Author(s):  
Meghan R. Sullivan ◽  
Kara A. Bernstein
Keyword(s):  
Homologous Recombination ◽  
Genome Stability ◽  
Homology Search ◽  
Model Organisms ◽  
Filament Formation ◽  
Dna Double Strand Breaks ◽  
Rad51 Paralogs ◽  
Human Rad51

The accurate repair of DNA is critical for genome stability and cancer prevention. DNA double-strand breaks are one of the most toxic lesions; however, they can be repaired using homologous recombination. Homologous recombination is a high-fidelity DNA repair pathway that uses a homologous template for repair. One central HR step is RAD51 nucleoprotein filament formation on the single-stranded DNA ends, which is a step required for the homology search and strand invasion steps of HR. RAD51 filament formation is tightly controlled by many positive and negative regulators, which are collectively termed the RAD51 mediators. The RAD51 mediators function to nucleate, elongate, stabilize, and disassemble RAD51 during repair. In model organisms, RAD51 paralogs are RAD51 mediator proteins that structurally resemble RAD51 and promote its HR activity. New functions for the RAD51 paralogs during replication and in RAD51 filament flexibility have recently been uncovered. Mutations in the human RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3, and SWSAP1) are found in a subset of breast and ovarian cancers. Despite their discovery three decades ago, few advances have been made in understanding the function of the human RAD51 paralogs. Here, we discuss the current perspective on the in vivo and in vitro function of the RAD51 paralogs, and their relationship with cancer in vertebrate models.

scholarly journals RAD-ical New Insights into RAD51 Regulation

2018 ◽  
Author(s):  
Meghan R. Sullivan ◽  
Kara A. Bernstein
Keyword(s):  
Genome Stability ◽  
Homology Search ◽  
Model Organisms ◽  
Filament Formation ◽  
Dna Double Strand Breaks ◽  
Current Perspective ◽  
Rad51 Paralogs ◽  
Human Rad51

Accurate repair of DNA is critical for genome stability and cancer prevention. DNA double-strand breaks are one of the most toxic lesions and can be repaired using homologous recombination (HR). HR is a high-fidelity DNA repair pathway that uses a homologous template for repair. One central HR step is RAD51 nucleoprotein filament formation on the single-stranded DNA ends, a step required for the homology search and strand invasion steps of HR. RAD51 filament formation is tightly controlled by many positive and negative regulators, collectively termed the RAD51 mediators. The RAD51 mediators function to nucleate, elongate, stabilize, and disassemble RAD51 during repair. In model organisms, RAD51 paralogs are RAD51 mediator proteins that structurally resemble RAD51 and promote its HR activity. New functions for the RAD51 paralogs during replication and in RAD51 filament flexibility have recently been uncovered. Mutations in the human RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3, and SWSAP1) are found in a subset of breast and ovarian cancers. Despite their discovery three decades ago, few advances have been made in understanding the function of the human RAD51 paralogs. Here we discuss the current perspective on the RAD51 paralogs in vivo and in vitro function and their relationship with cancer in vertebrate models.

scholarly journals Evidence for Simultaneous Protein Interactions between Human Rad51 Paralogs

2000 ◽  
Vol 275 (22) ◽  
pp. 16443-16449 ◽  
Author(s):  
David Schild ◽  
Yi-ching Lio ◽  
David W. Collins ◽  
Tswakai Tsomondo ◽  
David J. Chen
Keyword(s):  
Protein Interactions ◽  
Rad51 Paralogs ◽  
Human Rad51
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