title: DNA double-strand break repair pathway choice and cancer.
abstract: Since DNA double-strand breaks (DSBs) contribute to the genomic instability that drives cancer development, DSB repair pathways serve as important mechanisms for tumor suppression. Thus, genetic lesions, such as BRCA1 and BRCA2 mutations, that disrupt DSB repair are often associated with cancer susceptibility. In addition, recent evidence suggests that DSB "mis-repair", in which DSBs are resolved by an inappropriate repair pathway, can also promote genomic instability and presumably tumorigenesis. This notion has gained currency from recent cancer genome sequencing studies which have uncovered numerous chromosomal rearrangements harboring pathological DNA repair signatures. In this perspective, we discuss the factors that regulate DSB repair pathway choice and their consequences for genome stability and cancer.
authors.affiliation: Institute for Cancer Genetics & Department of Genetics and Development, Columbia University Medical Center, New York, NY, USA.
authors.forename: Tomas
authors.initials: T
authors.lastname: Aparicio
authors.affiliation: Institute for Cancer Genetics & Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Baer
authors.affiliation: Institute for Cancer Genetics & Department of Genetics and Development, Columbia University Medical Center, New York, NY, USA. Electronic address: jg130@columbia.edu.
authors.forename: Jean
authors.initials: J
authors.lastname: Gautier
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D011995:Recombination, Genetic; D015398:Signal Transduction; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1
keywords: 53BP1–BRCA1; DNA double strand break; DNA ends; Microhomology-mediated end joining; Repair pathway choice; Resection
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