The maintenance of genome integrity is essential to all life, but is particularly important to long-lived multicellular organisms, which are susceptible to cancer. DNA damage can take the form of base modifications, strand breaks, interstrand cross-links ...and other lesions. To deal with many types of damage, genomes have evolved multiple cellular defense mechanisms, including DNA repair and cell cycle checkpoint processes. Different pathways exist for specific kinds of DNA damage and the cell must have ways to decide which mechanism to use for a given lesion. These requirements imply that signaling networks not only sense the presence of DNA damage, but also receive specific input such as the chemical nature of the damage, the timing of the cell cycle, the type of cell and the location of damage on the DNA. BRCA1 is a tumor suppressor gene implicated in the predisposition to early onset breast and ovarian cancer. Loss of the tumor suppressor BRCA1 results in profound chromosomal instability. As a tumor suppressor, BRCA1 exerts a pleiotropic effect playing a role in the maintenance of genomic integrity. Several functions have also been ascribed to BRCA1 including double strand DNA break repair participating in genome surveillance transcription-coupled DNA repair, transcriptional regulation chromatin remodeling, and ubiquitin ligation and cell cycle checkpoint arrests. In cells, loss of BRCA1 function leads to spontaneous chromosome breakage and sensitivity to DNA damage. BASC (BRCA1-Associated Genome Surveillance Complex), a super complex of BRCA1 (Breast Cancer Susceptibility Protein-1), is key to recognizing and repairing DNA damage. This complex includes tumor suppressors and DNA damage repair proteins MSH2, MSH6, MLH1, ATM (Ataxia-Telangiectasia), BLM (Bloom syndrome), and the Rad50-MRE11 (Meiotic Recombination-11)-NBS1 (Nijmegen Breakage Syndrome-1) protein complex.
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