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APRIN is a cell cycle specific BRCA2‐interacting protein required for genome integrity and a predictor of outcome after chemotherapy in breast cancer
Author(s) -
Brough Rachel,
Bajrami Ilirjana,
Vatcheva Radost,
Natrajan Rachael,
ReisFilho Jorge S,
Lord Christopher J,
Ashworth Alan
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.490
Subject(s) - biology , breast cancer , brca2 protein , chemotherapy , outcome (game theory) , cell cycle , genetics , bioinformatics , cell cycle protein , cancer research , oncology , cancer , medicine , computational biology , mutation , gene , germline mutation , mathematics , mathematical economics
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.