期刊
MOLECULAR GENETICS AND GENOMICS
卷 285, 期 4, 页码 325-340出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00438-011-0612-5
关键词
Tumor-suppressor genes; Oncogenes; Development/abortion; Aging; Estrogens
资金
- Canadian Institutes of Health Research/Canadian Breast Cancer Research Alliance
- Canderel fellowship
- Faculte des etudes superieures
- Universite de Montreal
- Institut du Cancer de Montreal
EMSY links the BRCA2 pathway to sporadic breast/ovarian cancer. It encodes a nuclear protein that binds to the BRCA2 N-terminal domain implicated in chromatin/transcription regulation, but when sporadically amplified/overexpressed, increased EMSY level represses BRCA2 transactivation potential and induces chromosomal instability, mimicking the activity of BRCA2 mutations in the development of hereditary breast/ovarian cancer. In addition to chromatin/transcription regulation, EMSY may also play a role in the DNA-damage response, suggested by its ability to localize at chromatin sites of DNA damage/repair. This implies that EMSY overexpression may also repress BRCA2 in DNA-damage replication/checkpoint and recombination/repair, coordinated processes that also require its interacting proteins: PALB2, the partner and localizer of BRCA2; RPA, replication/checkpoint protein A; and RAD51, the inseparable recombination/repair enzyme. Here, using a well-characterized recombination/repair assay system, we demonstrate that a slight increase in EMSY level can indeed repress these two processes independently of transcriptional interference/repression. Since EMSY, RPA and PALB2 all bind to the same BRCA2 region, these findings further support a scenario
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