BRE/BRCC45 regulates CDC25A stability by recruiting USP7 in response to DNA damage.

Nat Commun 2018 02 7;9(1):537. Epub 2018 Feb 7.

Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA.

BRCA2 is essential for maintaining genomic integrity. BRCA2-deficient primary cells are either not viable or exhibit severe proliferation defects. Yet, BRCA2 deficiency contributes to tumorigenesis. It is believed that mutations in genes such as TRP53 allow BRCA2 heterozygous cells to overcome growth arrest when they undergo loss of heterozygosity. Here, we report the use of an insertional mutagenesis screen to identify a role for BRE (Brain and Reproductive organ Expressed, also known as BRCC45), known to be a part of the BRCA1-DNA damage sensing complex, in the survival of BRCA2-deficient mouse ES cells. Cell viability by BRE overexpression is mediated by deregulation of CDC25A phosphatase, a key cell cycle regulator and an oncogene. We show that BRE facilitates deubiquitylation of CDC25A by recruiting ubiquitin-specific-processing protease 7 (USP7) in the presence of DNA damage. Additionally, we uncovered the role of CDC25A in BRCA-mediated tumorigenesis, which can have implications in cancer treatment.

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http://dx.doi.org/10.1038/s41467-018-03020-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803202PMC
February 2018
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