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Rad51 Paralog Complexes BCDX2 and CX3 Act at Different Stages in the BRCA1-BRCA2-Dependent Homologous Recombination Pathway
Open accessAbstract
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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“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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Homologous Recombination and Human Health: The Roles of BRCA1, BRCA2, and Associated Proteins
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Pan-cancer landscape of homologous recombination deficiency.
Nguyen, L., W. M. Martens, J., Van Hoeck, A., & Cuppen, E. (2020) · Nature communications · doi:10.1038/s41467-020-19406-4 · Cited by 532
“Given that these 3 genes all belong to the RAD51 paralog complex BCDX2[24], the BRCA2-type HRD suggests that RAD51B and XRCC2 deficiency could have led to HRD in these patients.”
BackgroundLemacon, D. S., Jackson, J., Quinet, A., Brickner, J. R., Li, S., Yazinski, S. A., You, Z., Ira, G., Zou, L., Mosammaparast, N., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01180-5 · Cited by 429
Advances in genome editing through control of DNA repair pathways
Yeh, C. D., Richardson, C. D., & Corn, J. E. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0425-z · Cited by 425
Metadata
- Authors
- Chun, J., Buechelmaier, E. S., & Powell, S. N.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2013-01-01
- Volume
- 33
- Issue
- 2
- Pages
- 387-395
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC3554112
- 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
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- 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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