Regulation of DNA cross-link repair by the Fanconi anemia/BRCA pathway
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA
Abstract
The maintenance of genome stability is critical for survival, and its failure is often associated with tumorigenesis. The Fanconi anemia (FA) pathway is essential for the repair of DNA interstrand cross-links (ICLs), and a germline defect in the pathway results in FA, a cancer predisposition syndrome driven by genome instability. Central to this pathway is the monoubiquitination of FANCD2, which coordinates multiple DNA repair activities required for the resolution of ICLs. Recent studies have demonstrated how the FA pathway coordinates three critical DNA repair processes, including nucleolytic incision, translesion DNA synthesis (TLS), and homologous recombination (HR). Here, we review recent advances in our understanding of the downstream ICL repair steps initiated by ubiquitin-mediated FA pathway activation.
Keywords
- Fanconi anemia
- ubiquitination
- DNA interstrand cross-link
- DNA repair
- translesion DNA synthesis
- homologous recombination
Footnotes
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↵1 Corresponding author
E-mail alan_dandrea{at}dfci.harvard.edu
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.195248.112.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press