Regulation of the Histone H4 Monomethylase PR-Set7 by CRL4Cdt2-Mediated PCNA-Dependent Degradation during DNA Damage Journal Article
| Authors: | Oda, H.; Hübner, M. R.; Beck, D. B.; Vermeulen, M.; Hurwitz, J.; Spector, D. L.; Reinberg, D. |
| Article Title: | Regulation of the Histone H4 Monomethylase PR-Set7 by CRL4Cdt2-Mediated PCNA-Dependent Degradation during DNA Damage |
| 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 CRL4Cdt2-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. |
| Keywords: | signal transduction; controlled study; human cell; dna-binding proteins; mutant protein; ubiquitin; dna replication; mitosis; mammalia; animals; mice; dna damage; cell cycle s phase; proteasome endopeptidase complex; models, biological; protein degradation; protein binding; enzyme activation; cell line, tumor; nuclear proteins; protein processing, post-translational; histone methyltransferase; chromatin; histone-lysine n-methyltransferase; intracellular signaling peptides and proteins; genomics; protein structure, tertiary; cell cycle g2 phase; catalysis; ultraviolet rays; ubiquitin-protein ligases; histones; cell cycle g1 phase; s phase; s phase kinase associated protein 2; cullin proteins; biocatalysis; proliferating cell nuclear antigen; histone h4; enzyme stability; laser |
| Journal Title: | Molecular Cell |
| Volume: | 40 |
| Issue: | 3 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2010-11-12 |
| Start Page: | 364 |
| End Page: | 376 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2010.10.011 |
| PUBMED: | 21035370 |
| PROVIDER: | scopus |
| PMCID: | PMC2999913 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 7" - "Export Date: 20 April 2011" - "CODEN: MOCEF" - "Source: Scopus" |
