Journal
CANCER CELL
Volume 24, Issue 4, Pages 528-541Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2013.08.022
Keywords
-
Categories
Funding
- Agency for Science, Technology and Research (Singapore)
Ask authors/readers for more resources
Wip1 phosphatase is emerging as an important regulator of tumorigenesis, but no unifying mechanistic network has been proposed. We found that Wip1 plays a key role in the transcriptional regulation of heterochromatin-associated DNA sequences. Wip1 was required for epigenetic remodeling of repetitive DNA elements through regulation of BRCA1 interaction with HP1, the recruitment of DNA methyltransferases, and subsequent DNA methylation. Attenuation of ATM, in turn, reversed heterochromatin methylation. This mechanism was critical for the recruitment of the AID cytidine deaminase, and Wip1 levels strongly correlated with C-to-T substitutions and a total mutation load in primary breast cancers. We propose that Wip1 plays an important role in the regulation of global heterochromatin silencing and thus is critical in maintaining genome integrity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available