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Comment
. 2013 Apr;3(4):376-8.
doi: 10.1158/2159-8290.CD-13-0044.

BRCA1: a missing link in the Fanconi anemia/BRCA pathway

Alan D D'Andrea  1
Affiliations
Comment

BRCA1: a missing link in the Fanconi anemia/BRCA pathway

Alan D D'Andrea. Cancer Discov. 2013 Apr.

Abstract

Domchek and colleagues provide a case report of a 28-year-old woman with congenital abnormalities, inherited ovarian cancer, and carboplatin hypersensitivity. Interestingly, the woman had validated germline mutations in both BRCA1 alleles. These findings further implicate BRCA1 in the Fanconi anemia/BRCA pathway and have important implications for BRCA1 genetic testing.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest:

A.D. D’Andrea has no potential conflicts of interest.

Figures

Figure 1
Figure 1. BRCA1 cooperates in the Fanconi Anemia/BRCA1 pathway
The fifteen known FA proteins (A, B, C, D1, D2, E, F, G, I, J, L, M, N, O, P) cooperate in a common DNA repair pathway (in green). The pathway is activated when a replication fork stalls at a cisplatin interstrand crosslink (ICL). The FA core complex binds to the stalled fork, leading to monoubiquitination and recruitment of the I and D2 proteins. The downstream FA proteins (D2, N, J, and O) are recruited to DNA repair complexes. Additional proteins (in red), while not bonafide FA proteins, are also required for function of the FA pathway and for repair of DNA crosslinks. The BRCA1 protein is an FA-like protein and binds in a complex with at least three bonafide FA proteins. Biallelic mutations in BRCA1 (see text) result in an inherited ovarian cancer (FA-like) syndrome.
See this image and copyright information in PMC

Comment on

  • Biallelic deleterious BRCA1 mutations in a woman with early-onset ovarian cancer.
    Domchek SM, Tang J, Stopfer J, Lilli DR, Hamel N, Tischkowitz M, Monteiro AN, Messick TE, Powers J, Yonker A, Couch FJ, Goldgar DE, Davidson HR, Nathanson KL, Foulkes WD, Greenberg RA. Domchek SM, et al. Cancer Discov. 2013 Apr;3(4):399-405. doi: 10.1158/2159-8290.CD-12-0421. Epub 2012 Dec 26. Cancer Discov. 2013. PMID: 23269703 Free PMC article.

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