Homologous recombination in DNA repair and DNA damage tolerance

• Published in: Cell research Vol. 18; no. 1; pp. 99 - 113
• Main Authors: Li, Xuan, Heyer, Wolf-Dietrich
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2008; Nature Publishing Group
• Subjects: Animals; Biomedical and Life Sciences; Breast cancer; Cell Biology; Crossing Over, Genetic - physiology; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA Breaks, Double-Stranded; DNA Damage - physiology; DNA Repair - genetics; DNA Repair - physiology; DNA Replication - physiology; Etiology; Humans; Lesions; Life Sciences; Models, Biological; Mutagenesis - physiology; Mutation; Ovarian cancer; Protein Binding; Proteins; Rad51 Recombinase - metabolism; Recombination, Genetic - physiology; review; Sequence Homology; 损害机理; 脱氧核糖核酸; genome stability; interstrand crosslinks; stalled replication forks; homologous recombination; double-strand breaks; DNA repair
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2008.1

Homologous recombination （HR） comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks （DSBs） and interstrand 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.