Regulation of the Histone H4 Monomethylase PR-Set7 by CRL4 (Cdt2)-Mediated PCNA-Dependent Degradation during DNA Damage

Oda, H., Hübner, M. R. , Beck, D. B., Vermeulen, M., Hurwitz, J., Spector, D. L., Reinberg, D. (November 2010) Regulation of the Histone H4 Monomethylase PR-Set7 by CRL4 (Cdt2)-Mediated PCNA-Dependent Degradation during DNA Damage. Molecular Cell, 40 (3). pp. 364-376.

DOI: 10.1016/j.molcel.2010.10.011


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<sup>Cdt2</sup>-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. © 2010 Elsevier Inc. All rights reserved.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA methylation
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Microscopy Service
CSHL Post Doctoral Fellows
CSHL labs > Spector lab
CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
Depositing User: CSHL Librarian
Date: 12 November 2010
Date Deposited: 05 Oct 2011 14:59
Last Modified: 13 Oct 2015 16:00
PMCID: PMC2999913
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