Cited by 207DNA Repair MechanismsBRCA gene mutations in cancerPARP inhibition in cancer therapy

Rad51 Paralog Complexes BCDX2 and CX3 Act at Different Stages in the BRCA1-BRCA2-Dependent Homologous Recombination Pathway

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Chun, Jarin, Buechelmaier, Erika S., Powell, Simon N.·2013·Molecular and Cellular Biology

Abstract

The Rad51 paralogs are required for homologous recombination (HR) and the maintenance of genomic stability. The molecular mechanisms by which the five vertebrate Rad51 paralogs regulate HR and genomic integrity remain unclear. The Rad51 paralogs associate with one another in two distinct complexes: Rad51B-Rad51C-Rad51D-XRCC2 (BCDX2) and Rad51C-XRCC3 (CX3). We find that the BCDX2 and CX3 complexes act at different stages of the HR pathway. In response to DNA damage, the BCDX2 complex acts downstream of BRCA2 recruitment but upstream of Rad51 recruitment. In contrast, the CX3 complex acts downstream of Rad51 recruitment but still has a marked impact on the measured frequency of homologous recombination. Both complexes are epistatic with BRCA2 and synthetically lethal with Rad52. We conclude that human Rad51 paralogs facilitate BRCA2-Rad51-dependent homologous recombination at different stages in the pathway and function independently of Rad52.

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  • RAD51B and XRCC2 deficiency could have led to HRD in these patients.

    “Given that these three genes all belong to the RAD51 paralog complex BCDX223, the BRCA2-type HRD suggests that RAD51B and XRCC2 deficiency could have led to HRD in these patients.”

    From Pan-cancer landscape of homologous recombination deficiency. (2020) · cites this paper as [23]

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Authors
Chun, J., Buechelmaier, E. S., & Powell, S. N.
Affiliations
Memorial Sloan Kettering Cancer Center (US)
Venue
Molecular and Cellular Biology
Published
2013-01-01
Volume
33
Issue
2
Pages
387-395
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2098812676
Cited by
207
References
42
Citations by year
2026: 10 · 2025: 8 · 2024: 8 · 2023: 21 · 2022: 14 · 2021: 22 · 2020: 16 · 2019: 19 · 2018: 22 · 2017: 8 · 2016: 21 · 2015: 13 · 2014: 14 · 2013: 9 · 2012: 1
FWCI
4.76
Type
journal article
Language
en
Open access
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Public Health Service
  • National Cancer Institute (R01CA107640, R01CA169306, CA107640, P30CA008748)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
  • Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Keywords
RAD51 paralogs, homologous recombination, BRCA1, BRCA2, RAD52, epistasis, synthetic lethality, DNA damage response, genome stability
MeSH terms
Cell Line, DNA Damage, DNA-Binding Proteins, Epistasis, Genetic, Humans, Microscopy, Confocal, BRCA2 Protein, Ubiquitin-Protein Ligases, Rad51 Recombinase, Rad52 DNA Repair and Recombination Protein, Homologous Recombination, MCF-7 Cells

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