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RAD-ical New Insights into RAD51 Regulation

Sullivan, Meghan R. and Bernstein, Kara A. (2018) RAD-ical New Insights into RAD51 Regulation. Genes, 9 (12). p. 629. ISSN 2073-4425

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Abstract

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.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Sullivan, Meghan R.mrs149@pitt.edumrs149
Bernstein, Kara A.karab@pitt.edukarab
Date: 13 December 2018
Date Type: Publication
Journal or Publication Title: Genes
Volume: 9
Number: 12
Publisher: MDPI AG
Page Range: p. 629
DOI or Unique Handle: 10.3390/genes9120629
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
Uncontrolled Keywords: homologous recombination, RAD51 paralogs, BRCA1, BRCA2, RAD51B, RAD51C, RAD51D, XRCC2, XRCC3, Shu complex, cancer
ISSN: 2073-4425
Official URL: http://dx.doi.org/10.3390/genes9120629
Funders: National Institutes of Health, American Cancer Society, Stand Up to Cancer
Article Type: Review
Date Deposited: 14 Dec 2021 19:35
Last Modified: 14 Dec 2021 19:35
URI: http://d-scholarship.pitt.edu/id/eprint/42101

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