The EMSY threonine 207 phospho-site is required for EMSYdriven suppression of DNA damage repair Journal Article
| Authors: | Jelinic, P.; Eccles, L. A.; Tseng, J.; Cybulska, P.; Wielgos, M.; Powell, S. N.; Levine, D. A. |
| Article Title: | The EMSY threonine 207 phospho-site is required for EMSYdriven suppression of DNA damage repair |
| Abstract: | 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. |
| Keywords: | dna repair; brca2; pka; brcaness; emsy |
| Journal Title: | Oncotarget |
| Volume: | 8 |
| Issue: | 8 |
| ISSN: | 1949-2553 |
| Publisher: | Impact Journals |
| Date Published: | 2017-02-21 |
| Start Page: | 13792 |
| End Page: | 13804 |
| Language: | English |
| DOI: | 10.18632/oncotarget.14637 |
| PROVIDER: | scopus |
| PUBMED: | 28099152 |
| PMCID: | PMC5355139 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 April 2017 -- Source: Scopus |
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