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Nucleic Acids Res. 2016 Dec 15;44(22):10879-10897. Epub 2016 Oct 24.

Roles for APRIN (PDS5B) in homologous recombination and in ovarian cancer prediction.

Author information

1
Genome Stability Laboratory, CHU de Québec Research Center, HDQ Pavilion, Oncology Axis, 9 McMahon, Québec City, QC G1R 2J6, Canada.
2
Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Québec City, QC G1V 0A6, Canada.
3
Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada; Institut du cancer de Montréal, Montréal, QC H2X 0A9, Canada.
4
Department of Medicine, Université de Montréal, Montréal, QC H2X 0A9, Canada.
5
Institut de Recherches Cliniques de Montréal and Department of Medicine, Université de Montréal, Montréal, Québec H2W 1R7, Canada.
6
Dalhousie University, Faculty of Medicine, Department of Pathology, Halifax, NS B3H 4R2, Canada.
7
Dalhousie University, Faculty of Medicine, Departments of Microbiology and Immunology, Pediatrics and Pathology, Halifax, NS B3H 4R2, Canada.
8
Genome Stability Laboratory, CHU de Québec Research Center, HDQ Pavilion, Oncology Axis, 9 McMahon, Québec City, QC G1R 2J6, Canada Jean-Yves.Masson@fmed.ulaval.ca.

Abstract

APRIN (PDS5 cohesin associated factor B) interacts with both the cohesin complex and the BRCA2 tumor suppressor. How APRIN influences cohesion and DNA repair processes is not well understood. Here, we show that APRIN is recruited to DNA damage sites. We find that APRIN interacts directly with RAD51, PALB2 and BRCA2. APRIN stimulates RAD51-mediated DNA strand invasion. APRIN also binds DNA with an affinity for D-loop structures and single-strand (ss) DNA. APRIN is a new homologous recombination (HR) mediator as it counteracts the RPA inhibitory effect on RAD51 loading to ssDNA. We show that APRIN strongly improves the annealing of complementary-strand DNA and that it can stimulate this process in synergy with BRCA2. Unlike cohesin constituents, its depletion has no impact on class switch recombination, supporting a specific role for this protein in HR. Furthermore, we show that low APRIN expression levels correlate with a better survival in ovarian cancer patients and that APRIN depletion sensitizes cells to the PARP inhibitor Olaparib in xenografted zebrafish. Our findings establish APRIN as an important and specific actor of HR, with cohesin-independent functions.

PMID:
27924011
PMCID:
PMC5159559
DOI:
10.1093/nar/gkw921
[Indexed for MEDLINE]
Free PMC Article

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