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Titles listPR-Set7-dependent lysine methylation ensures genome replication and stability through S phase
Titles listPR-Set7-dependent lysine methylation ensures genome replication and stability through S phase
Scientific Article
unige:43624 
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PR-Set7-dependent lysine methylation ensures genome replication and stability through S phase |
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| Authors | ||
| Published in | The Journal of Cell Biology. 2007, vol. 179, no. 7, p. 1413-26 | |
| 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. | |
| Keywords | Ataxia Telangiectasia Mutated Proteins — Cell Cycle Proteins/genetics — Cell Line, Tumor — DNA Damage/genetics — DNA Repair/genetics — DNA Replication/genetics — DNA-Binding Proteins/genetics — Down-Regulation/genetics — Genomic Instability/genetics — Histone-Lysine N-Methyltransferase/genetics — Histones/genetics/metabolism — Humans — Lysine/metabolism — Methylation — Protein Processing, Post-Translational/physiology — Protein-Serine-Threonine Kinases/genetics — RNA, Small Interfering — S Phase/genetics — Tumor Suppressor Proteins/genetics | |
| Identifiers | PMID: 18158331 | |
| Full text | ||
| Citation (ISO format) | TARDAT, Mathieu et al. PR-Set7-dependent lysine methylation ensures genome replication and stability through S phase. In: The Journal of Cell Biology, 2007, vol. 179, n° 7, p. 1413-26. doi: 10.1083/jcb.200706179 https://archive-ouverte.unige.ch/unige:43624 |
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