Homology-directed repair and the role of BRCA1, BRCA2, and related proteins in genome integrity and cancer Journal Article

   

Authors:	Chen, C. C.; Feng, W.; Lim, P. X.; Kass, E. M.; Jasin, M.
Article Title:	Homology-directed repair and the role of BRCA1, BRCA2, and related proteins in genome integrity and cancer
Abstract:	Germ-line and somatic mutations in genes that promote homology-directed repair (HDR), especially BRCA1 and BRCA2, are frequently observed in several cancers, in particular, breast and ovary but also prostate and other cancers. HDR is critical for the error-free repair of DNA double-strand breaks and other lesions, and HDR factors also protect stalled replication forks. As a result, loss of BRCA1 or BRCA2 poses significant risks to genome integrity, leading not only to cancer predisposition but also to sensitivity to DNA-damaging agents, affecting therapeutic approaches. Here we review recent advances in our understanding of BRCA1 and BRCA2, including how they genetically interact with other repair factors, how they protect stalled replication forks, how they affect the response to aldehydes, and how loss of their functions links to mutation signatures. Importantly, given the recent advances with poly(ADP-ribose) polymerase inhibitors (PARPi) for the treatment of HDR-deficient tumors, we discuss mechanisms by which BRCA-deficient tumors acquire resistance to PARPi and other agents.
Keywords:	homologous recombination; brca1; brca2; lethality; double-strand break repair; atm; replication; ataxia-telangiectasia; somatic mutations; dna-damage response; forks; parp inhibitor; fanconi-anemia; strand-break repair; early embryonic; cell-free dna; telangiectasia mutated atm; replication fork protection
Journal Title:	Annual Review of Cancer Biology
Volume:	2
ISSN:	2472-3428
Publisher:	Annual Reviews
Date Published:	2018-01-01
Start Page:	313
End Page:	336
Language:	English
ACCESSION:	WOS:000462706100017
PROVIDER:	wos
PMCID:	PMC6193498
PUBMED:	30345412
DOI:	10.1146/annurev-cancerbio-030617-050502
Notes:	Source: Wos

https://synapse.mskcc.org/synapse/works/has_related_data_chk/145837