Homologous repair of DNA damage and tumorigenesis: the BRCA connection.
Homologous recombination has been recognized in recent years to be an important DNA repair pathway in mammalian cells, for such damage as chromosomal double-strand breaks. Cells mutated for the genes involved in the hereditary breast and ovarian cancer susceptibility syndromes, i.e. BRCA1 and BRCA2, show defects in DNA repair by homologous recombination, implicating this repair pathway in protecting individuals against tumorigenesis. This review summarizes recent advances in our understanding of BRCA1 and BRCA2 in DNA repair, as well as insight into these proteins gleaned from structure determination of domains of these proteins and the broader evolutionary conservation than previously appreciated.
Jasin
Maria
M
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. m-jasin@ski.mskcc.org
D000595:Amino Acid Sequence; D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D024682:BRCA2 Protein / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D051135:Rad51 Recombinase; D011995:Recombination, Genetic; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases; C495153:RAD51 protein, human; D051135:Rad51 Recombinase