Priority Research Papers:

The EMSY threonine 207 phospho-site is required for EMSYdriven suppression of DNA damage repair

Petar Jelinic, Laura A. Eccles, Jill Tseng, Paulina Cybulska, Monicka Wielgos, Simon N. Powell and Douglas A. Levine _

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Oncotarget. 2017; 8:13792-13804. https://doi.org/10.18632/oncotarget.14637

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Petar Jelinic1, Laura A. Eccles2, Jill Tseng3, Paulina Cybulska3, Monicka Wielgos1, Simon N. Powell2, Douglas A. Levine1

1Laura and Isaac Perlmutter Cancer Center, Division of Gynecologic Oncology, Department of OB/GYN, NYU Langone Medical Center, New York, USA

2Departments of Radiation Oncology and Molecular Biology, Memorial Sloan Kettering Cancer Center, New York, USA

3Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA

Correspondence to:

Douglas A. Levine, email: [email protected]

Keywords: EMSY, BRCAness, PKA, BRCA2, DNA repair

Received: September 02, 2016     Accepted: January 04, 2017     Published: January 13, 2017


BRCA1 and BRCA2 are essential for the repair of double-strand DNA breaks, and alterations in these genes are a hallmark of breast and ovarian carcinomas. Other functionally related genes may also play important roles in carcinogenesis. Amplification of EMSY, a putative BRCAness gene, has been suggested to impair DNA damage repair by suppressing BRCA2 function. We employed direct repeat GFP (DR-GFP) and RAD51 foci formation assays to show that EMSY overexpression impairs the repair of damaged DNA, suggesting that EMSY belongs to the family of BRCAness proteins. We also identified a novel phospho-site at threonine 207 (T207) and demonstrated its role in EMSY-driven suppression of DNA damage repair. In vitro kinase assays established that protein kinase A (PKA) directly phosphorylates the T207 phospho-site. Immunoprecipitation experiments suggest that EMSY-driven suppression of DNA damage repair is a BRCA2-independent process. The data also suggest that EMSY amplification is a BRCAness feature, and may help to expand the population of patients who could benefit from targeted therapies that are also effective in BRCA1/2-mutant cancers.

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