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

Anthony M. Couturier; Hubert Fleury; Anne Marie Patenaude; Victoria L. Bentley; Amélie Rodrigue; Yan Coulombe; Joshi Niraj; Joris Pauty; Jason N. Berman; Graham Dellaire; Javier M. Di Noia; Anne Marie Mes-Masson; Jean Yves Masson

doi:10.1093/nar/gkw921

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

Anthony M. Couturier, Hubert Fleury, Anne Marie Patenaude, Victoria L. Bentley, Amélie Rodrigue, Yan Coulombe, Joshi Niraj, Joris Pauty, Jason N. Berman, Graham Dellaire, Javier M. Di Noia, Anne Marie Mes-Masson, Jean Yves Masson

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Resumen

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.

Idioma original	English
Páginas (desde-hasta)	10879-10897
Número de páginas	19
Publicación	Nucleic Acids Research
Volumen	44
N.º	22
DOI	https://doi.org/10.1093/nar/gkw921
Estado	Published - dic. 2016

Nota bibliográfica

Funding Information:
Luc Bélanger Scholarship (to A.M.C.); Michèle St- Pierre - Institut du cancer de Montréal Research Fund (to H.F.); Nova Scotia Health Research Foundation (NSHRF) Scholar Award (to V.L.B.); Beatrice Hunter Cancer Research Institute (BHCRI) Trainee Award with funds provided by the CIBC, as part of The Terry Fox Foundation Strategic Health Research Training Program in Cancer Research at CIHR (to V.L.B.); HOG Scholarship (Oncology Axis, CHU de Québec) (to J.N.); Ovarian Cancer Canada Trainee Travel Award (to J.P.); FRQS Chercheur National Investigator and FRQS chair in genome stability (to J.Y.M.); BHCRI (to G.D., J.N.B.); Canada Research Chair tier 2 (to J.M.D.N.); Cancer Research Society (CRS); Canadian Cancer Society Research Institute (CCSRI) [702806](to J.Y.M.); Collaborative Health Research Project (CHRP) Operating Grant (to G.D., J.N.B.); Natural Sciences and Engineering Research Council (NSERC); Canadian Institutes of Health Research (CIHR); CIHR Grant [MOP-130535 to J.M.D.N.]. Funding for open access charge: CHIR. Tumor banking was supported by the Banque de tissus et données of the Réseau de recherche sur le cancer of the Fond de recherche du Québec - Santé (FRQS), associated with the Canadian Tumor Repository Network (CTRNet). H.F., A-M.M-M. and D.M.P. are researchers of the Centre de recherche du CHUM which receives support from the FRQS.

Publisher Copyright:
© The Author(s) 2016.

ASJC Scopus Subject Areas

Genetics

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title = "Roles for APRIN (PDS5B) in homologous recombination and in ovarian cancer prediction",

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.",

author = "Couturier, {Anthony M.} and Hubert Fleury and Patenaude, {Anne Marie} and Bentley, {Victoria L.} and Am{\'e}lie Rodrigue and Yan Coulombe and Joshi Niraj and Joris Pauty and Berman, {Jason N.} and Graham Dellaire and {Di Noia}, {Javier M.} and Mes-Masson, {Anne Marie} and Masson, {Jean Yves}",

note = "Funding Information: Luc B{\'e}langer Scholarship (to A.M.C.); Mich{\`e}le St- Pierre - Institut du cancer de Montr{\'e}al Research Fund (to H.F.); Nova Scotia Health Research Foundation (NSHRF) Scholar Award (to V.L.B.); Beatrice Hunter Cancer Research Institute (BHCRI) Trainee Award with funds provided by the CIBC, as part of The Terry Fox Foundation Strategic Health Research Training Program in Cancer Research at CIHR (to V.L.B.); HOG Scholarship (Oncology Axis, CHU de Qu{\'e}bec) (to J.N.); Ovarian Cancer Canada Trainee Travel Award (to J.P.); FRQS Chercheur National Investigator and FRQS chair in genome stability (to J.Y.M.); BHCRI (to G.D., J.N.B.); Canada Research Chair tier 2 (to J.M.D.N.); Cancer Research Society (CRS); Canadian Cancer Society Research Institute (CCSRI) [702806](to J.Y.M.); Collaborative Health Research Project (CHRP) Operating Grant (to G.D., J.N.B.); Natural Sciences and Engineering Research Council (NSERC); Canadian Institutes of Health Research (CIHR); CIHR Grant [MOP-130535 to J.M.D.N.]. Funding for open access charge: CHIR. Tumor banking was supported by the Banque de tissus et donn{\'e}es of the R{\'e}seau de recherche sur le cancer of the Fond de recherche du Qu{\'e}bec - Sant{\'e} (FRQS), associated with the Canadian Tumor Repository Network (CTRNet). H.F., A-M.M-M. and D.M.P. are researchers of the Centre de recherche du CHUM which receives support from the FRQS. Publisher Copyright: {\textcopyright} The Author(s) 2016.",

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doi = "10.1093/nar/gkw921",

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AU - Couturier, Anthony M.

AU - Fleury, Hubert

AU - Patenaude, Anne Marie

AU - Bentley, Victoria L.

AU - Rodrigue, Amélie

AU - Coulombe, Yan

AU - Niraj, Joshi

AU - Pauty, Joris

AU - Berman, Jason N.

AU - Dellaire, Graham

AU - Di Noia, Javier M.

AU - Mes-Masson, Anne Marie

AU - Masson, Jean Yves

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PY - 2016/12

Y1 - 2016/12

N2 - 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.

AB - 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.

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

Resumen

Nota bibliográfica

ASJC Scopus Subject Areas

ODS de las Naciones Unidas

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