Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2012 Apr 27;46(2):111-2.
doi: 10.1016/j.molcel.2012.04.010.

A novel function for BRCA1 in crosslink repair

David T Long  1 , Johannes C Walter
Affiliations
Comment

A novel function for BRCA1 in crosslink repair

David T Long et al. Mol Cell. .

Abstract

In this issue of Molecular Cell, Bunting et al. (2012) provide new evidence that BRCA1 plays an important role in DNA interstrand crosslink repair that is distinct from its established function in promoting DNA end resection during homologous recombination.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Possible roles for BRCA1 in ICL repair
(A) Replication fork stalling at an ICL leads to FANCI-FANCD2 ubiquitylation, which promotes DNA incisions that unhook the crosslink and create a DSB in one sister chromatid. In the absence of BRCA1, FANCD2 localization is suppressed by Ku. (B) After DNA incisions, the bottom sister chromatid is restored by translesion DNA synthesis (TLS) and nucleotide excision repair (NER), and the ends of the DSB are resected to produce 3’ ssDNA overhangs. In the absence of BRCA1, 53BP1 inhibits resection of DNA ends, thereby favoring error-prone repair by NHEJ that can promote genomic instability. Rad51 promotes strand exchange between the sister chromatids (C), resulting in two fully intact DNA duplexes (D).
See this image and copyright information in PMC

Comment on

References

    1. Adamo A, Collis SJ, Adelman CA, Silva N, Horejsi Z, Ward JD, Martinez-Perez E, Boulton SJ, La Volpe A. Preventing nonhomologous end joining suppresses DNA repair defects of Fanconi anemia. Molecular cell. 2010;39:25–35. - PubMed
    1. Bunting SF, Callen E, Kozak ML, Kim JM, Wong N, Lopez-Contreras AJ, Ludwig T, Baer R, Faryabi RB, Malhowski A, et al. BRCA1 Functions Independently of Homologous Recombination in DNA Interstrand Crosslink Repair. Molecular cell. 2012 - PMC - PubMed
    1. Bunting SF, Callen E, Wong N, Chen HT, Polato F, Gunn A, Bothmer A, Feldhahn N, Fernandez-Capetillo O, Cao L, et al. 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell. 2010;141:243–254. - PMC - PubMed
    1. Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M, D'Andrea AD. Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Mol Cell. 2001;7:249–262. - PubMed
    1. Knipscheer P, Raschle M, Smogorzewska A, Enoiu M, Ho TV, Scharer OD, Elledge SJ, Walter JC. The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair. Science. 2009;326:1698–1701. - PMC - PubMed

LinkOut - more resources