Journal
EMBO JOURNAL
Volume 31, Issue 5, Pages 1160-1176Publisher
WILEY
DOI: 10.1038/emboj.2011.490
Keywords
BRCA2; breast cancer; DNA repair
Categories
Funding
- Breakthrough Breast Cancer
- Cancer Research UK
Ask authors/readers for more resources
Mutations in BRCA2 confer an increased risk of cancer development, at least in part because the BRCA2 protein is required for the maintenance of genomic integrity. Here, we use proteomic profiling to identify APRIN (PDS5B), a cohesion-associated protein, as a BRCA2-associated protein. After exposure of cells to hydroxyurea or aphidicolin, APRIN and other cohesin components associate with BRCA2 in early S-phase. We demonstrate that APRIN expression is required for the normal response to DNA-damaging agents, the nuclear localisation of RAD51 and BRCA2 and efficient homologous recombination. The clinical significance of these findings is indicated by the observation that the BRCA2/APRIN interaction is compromised by BRCA2 missense variants of previously unknown significance and that APRIN expression levels are associated with histological grade in breast cancer and the outcome of breast cancer patients treated with DNA-damaging chemotherapy. The EMBO Journal (2012) 31, 1160-1176. doi: 10.1038/emboj.2011.490; Published online 31 January 2012
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available