Journal
MOLECULAR CELL
Volume 40, Issue 3, Pages 364-376Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2010.10.011
Keywords
-
Categories
Funding
- NIH [GM64844, GM42694]
- HHMI
- European Molecular Biology Organization (EMBO [ALTF 160-2005]
- German Academic Exchange Service (DAAD)
Ask authors/readers for more resources
The histone methyltransferase PR-Set7/Set8 is the sole enzyme that catalyzes monomethylation of histone H4 at K20 (H4K20me1). Previous reports document disparate evidence regarding PR-Set7 expression during the cell cycle, the biological relevance of PR-Set7 interaction with PCNA, and its role in the cell. We find that PR-Set7 is indeed undetectable during S phase and instead is detected during late G2, mitosis, and early Gl. PR-Set7 is transiently recruited to laser-induced DNA damage sites through its interaction with PCNA, after which 53BP1 is recruited dependent on PR-Set7 catalytic activity. During the DNA damage response, PR-Set7 interaction with PCNA through a specialized PIP degron domain targets it for PCNA-coupled CRL4(cdt2)-dependent proteolysis. PR-Set7 mutant in its PIP degron is now detectable during S phase, during which the mutant protein accumulates. Outside the chromatin context, Skp2 promotes PR-Set7 degradation as well. These findings demonstrate a stringent spatiotemporal control of PR-Set7 that is essential for preserving the genomic integrity of mammalian cells.
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