Abstract：
: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 G1. 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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Oda H,Hübner MR,Beck DB,Vermeulen M,Hurwitz J,Spector DL,Reinberg Ddoi
10.1016/j.molcel.2010.10.011subject
Has Abstractpub_date
2010-11-12 00:00:00pages
364-76issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(10)00787-2journal_volume
40pub_type
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