Journal
ONCOGENE
Volume 29, Issue 17, Pages 2499-2508Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2010.18
Keywords
BRCA1; FANCJ; DNA repair
Funding
- NIH [R01 CA129514-01A1]
- NATIONAL CANCER INSTITUTE [R01CA129514] Funding Source: NIH RePORTER
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BRCA1 and the DNA helicase FANCJ (also known as BACH1 or BRIP1) have common functions in breast cancer suppression and DNA repair. However, the functional significance of the direct interaction between BRCA1 and FANCJ remains unclear. Here, we have discovered that BRCA1 binding to FANCJ regulates DNA damage repair choice. Thus, when FANCJ binding to BRCA1 is ablated, the molecular mechanism chosen for the repair of damaged DNA is dramatically altered. Specifically, a FANCJ protein that cannot be phosphorylated at serine 990 or bind BRCA1 inhibits DNA repair via homologous recombination and promotes pol eta-dependent bypass. Furthermore, the pol eta-dependent bypass promoted by FANCJ requires the direct binding to the mismatch repair (MMR) protein, MLH1. Together, our findings implicate that in human cells BRCA1 binding to FANCJ is critical to regulate DNA repair choice and promote genomic stability. Moreover, unregulated FANCJ function could be associated with cancer and/or chemoresistance. Oncogene (2010) 29, 2499-2508; doi:10.1038/onc.2010.18; published online 22 February 2010
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