| Added by | eric_julien |
|---|---|
| Group name | EquipeEJ |
| Item Type | Journal Article |
| Title | Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing |
| Creator | Shoaib et al. |
| Author | Muhammad Shoaib |
| Author | David Walter |
| Author | Peter J. Gillespie |
| Author | Fanny Izard |
| Author | Birthe Fahrenkrog |
| Author | David Lleres |
| Author | Mads Lerdrup |
| Author | Jens Vilstrup Johansen |
| Author | Klaus Hansen |
| Author | Eric Julien |
| Author | J. Julian Blow |
| Author | Claus S. Sřrensen |
| Abstract | The decompaction and re-establishment of chromatin organization immediately after mitosis is essential for genome regulation. Mechanisms underlying chromatin structure control in daughter cells are not fully understood. Here we show that a chromatin compaction threshold in cells exiting mitosis ensures genome integrity by limiting replication licensing in G1 phase. Upon mitotic exit, chromatin relaxation is controlled by SET8-dependent methylation of histone H4 on lysine 20. In the absence of either SET8 or H4K20 residue, substantial genome-wide chromatin decompaction occurs allowing excessive loading of the origin recognition complex (ORC) in the daughter cells. ORC overloading stimulates aberrant recruitment of the MCM2-7 complex that promotes single-stranded DNA formation and DNA damage. Restoring chromatin compaction restrains excess replication licensing and loss of genome integrity. Our findings identify a cell cycle-specific mechanism whereby fine-tuned chromatin relaxation suppresses excessive detrimental replication licensing and maintains genome integrity at the cellular transition from mitosis to G1 phase. |
| Publication | Nature Communications |
| Volume | 9 |
| Issue | 1 |
| Pages | 3704 |
| Date | Sep 12, 2018 |
| Journal Abbr | Nat Commun |
| Language | eng |
| DOI | 10.1038/s41467-018-06066-8 |
| ISSN | 2041-1723 |
| Library Catalog | PubMed |
| Extra | PMID: 30209253 PMCID: PMC6135857 |
| Tags | epigenmed, ligue, original |
| Date Added | 2018/09/26 - 15:46:20 |
| Date Modified | 2019/11/29 - 16:50:51 |
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