| Added by | eric_julien |
|---|---|
| Group name | EquipeEJ |
| Item Type | Journal Article |
| Title | PR-Set7-dependent lysine methylation ensures genome replication and stability through S phase |
| Creator | Tardat et al. |
| Author | Mathieu Tardat |
| Author | Rabih Murr |
| Author | Zdenko Herceg |
| Author | Claude Sardet |
| Author | Eric Julien |
| Abstract | PR-Set7/SET8 is a histone H4-lysine 20 methyltransferase required for normal cell proliferation. However, the exact functions of this enzyme remain to be determined. In this study, we show that human PR-Set7 functions during S phase to regulate cellular proliferation. PR-Set7 associates with replication foci and maintains the bulk of H4-K20 mono- and trimethylation. Consistent with a function in chromosome dynamics during S phase, inhibition of PR-Set7 methyltransferase activity by small hairpin RNA causes a replicative stress characterized by alterations in replication fork velocity and origin firing. This stress is accompanied by massive induction of DNA strand breaks followed by a robust DNA damage response. The DNA damage response includes the activation of ataxia telangiectasia mutated and ataxia telangiectasia related kinase-mediated pathways, which, in turn, leads to p53-mediated growth arrest to avoid aberrant chromosome behavior after improper DNA replication. Collectively, these data indicate that PR-Set7-dependent lysine methylation during S phase is an essential posttranslational mechanism that ensures genome replication and stability. |
| Publication | The Journal of Cell Biology |
| Volume | 179 |
| Issue | 7 |
| Pages | 1413-1426 |
| Date | Dec 31, 2007 |
| Journal Abbr | J. Cell Biol. |
| Language | eng |
| DOI | 10.1083/jcb.200706179 |
| ISSN | 1540-8140 |
| Library Catalog | PubMed |
| Extra | PMID: 18158331 PMCID: PMC2373513 |
| Tags | Ataxia Telangiectasia Mutated Proteins, Cell Cycle Proteins, Cell Line, Tumor, DNA Repair, DNA Replication, DNA-Binding Proteins, Down-Regulation, Genomic Instability, Histone-Lysine N-Methyltransferase, Histones, Humans, Lysine, Methylation, Protein Processing, Post-Translational, Protein-Serine-Threonine Kinases, RNA, Small Interfering, S Phase, Tumor Suppressor Proteins |
| Date Added | 2018/09/26 - 15:50:02 |
| Date Modified | 2018/09/26 - 15:50:02 |
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