Journal
CELL RESEARCH
Volume 18, Issue 1, Pages 99-113Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cr.2008.1
Keywords
DNA repair; double-strand breaks; genome stability; homologous recombination; interstrand crosslinks; stalled replication forks
Categories
Funding
- NATIONAL CANCER INSTITUTE [R01CA092276] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM058015] Funding Source: NIH RePORTER
- NCI NIH HHS [R01 CA092276-10, R01 CA092276] Funding Source: Medline
- NIGMS NIH HHS [R01 GM058015, R01 GM058015-10] Funding Source: Medline
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Homologous recombination (HR) comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks (DSBs) and inter-strand crosslinks (ICLs). In addition, recombination provides critical support for DNA replication in the recovery of stalled or broken replication forks, contributing to tolerance of DNA damage. A central core of proteins, most critically the RecA homolog Rad51, catalyzes the key reactions that typify HR: homology search and DNA strand invasion. The diverse functions of recombination are reflected in the need for context-specific factors that perform supplemental functions in conjunction with the core proteins. The inability to properly repair complex DNA damage and resolve DNA replication stress leads to genomic instability and contributes to cancer etiology. Mutations in the BRCA2 recombination gene cause predisposition to breast and ovarian cancer as well as Fanconi anemia, a cancer predisposition syndrome characterized by a defect in the repair of DNA interstrand crosslinks. The cellular functions of recombination are also germane to DNA-based treatment modalities of cancer, which target replicating cells by the direct or indirect induction of DNA lesions that are substrates for recombination pathways. This review focuses on mechanistic aspects of HR relating to DSB and ICL repair as well as replication fork support.
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