BRCA1 cooperates in the Fanconi anemia/BRCA1 pathway.

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Presentation transcript:

BRCA1 cooperates in the Fanconi anemia/BRCA1 pathway. BRCA1 cooperates in the Fanconi anemia/BRCA1 pathway. The fifteen known Fanconi anemia proteins (A, B, C, D1, D2, E, F, G, I, J, L, M, N, O, P) cooperate in a common DNA repair pathway (green). The pathway is activated when a replication fork stalls at a cisplatin interstrand cross-link (ICL). The Fanconi anemia core complex binds to the stalled fork, leading to monoubiquitination and recruitment of the I and D2 proteins. The downstream Fanconi anemia proteins (D2, N, J, and O) are recruited to DNA repair complexes. Additional proteins (red), while not bona fide Fanconi anemia proteins, are also required for function of the Fanconi anemia pathway and for repair of DNA cross-links. The BRCA1 protein is a Fanconi anemia-like protein and binds in a complex with at least 3 bonafide Fanconi anemia proteins. Biallelic mutations in BRCA1 (see text) result in an inherited ovarian cancer (Fanconi anemia-like) syndrome. Alan D. D'Andrea Cancer Discovery 2013;3:376-378 ©2013 by American Association for Cancer Research