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Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing
- Source :
- Nature communications, 9 (1, Shoaib, M, Walter, D, Gillespie, P J, Izard, F, Fahrenkrog, B, Lleres, D, Lerdrup, M, Johansen, J V, Hansen, K, Julien, E, Blow, J J & Sørensen, C S 2018, ' Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing ', Nature Communications, vol. 9, no. 1, 3704, pp. 1-11 . https://doi.org/10.1038/s41467-018-06066-8, Nature Communications, Nature Communications, Nature Publishing Group, 2018, 9, pp.3704. ⟨10.1038/s41467-018-06066-8⟩, Nature Communications, Vol 9, Iss 1, Pp 1-11 (2018), Nature Communications, 2018, 9, pp.3704. ⟨10.1038/s41467-018-06066-8⟩
- Publication Year :
- 2018
-
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.<br />SCOPUS: ar.j<br />info:eu-repo/semantics/published
- Subjects :
- DNA Replication
0301 basic medicine
MESH: Cell Line, Tumor
Cell division
Science
General Physics and Astronomy
MESH: DNA Replication
MESH: Flow Cytometry
MESH: Microscopy, Fluorescence
Article
General Biochemistry, Genetics and Molecular Biology
MESH: Chromatin
Histones
Histone H4
03 medical and health sciences
Cell Line, Tumor
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
MESH: RNA, Small Interfering
Humans
Chimie
RNA, Small Interfering
lcsh:Science
Mitosis
MESH: DNA Damage
MESH: Histones
MESH: Humans
Multidisciplinary
biology
Chemistry
Physique
DNA replication
General Chemistry
Astronomie
Flow Cytometry
Chromatin
Cell biology
Technologie de l'environnement, contrôle de la pollution
030104 developmental biology
Histone
Microscopy, Fluorescence
Mitotic exit
biology.protein
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
Origin recognition complex
lcsh:Q
DNA Damage
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature communications, 9 (1, Shoaib, M, Walter, D, Gillespie, P J, Izard, F, Fahrenkrog, B, Lleres, D, Lerdrup, M, Johansen, J V, Hansen, K, Julien, E, Blow, J J & Sørensen, C S 2018, ' Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing ', Nature Communications, vol. 9, no. 1, 3704, pp. 1-11 . https://doi.org/10.1038/s41467-018-06066-8, Nature Communications, Nature Communications, Nature Publishing Group, 2018, 9, pp.3704. ⟨10.1038/s41467-018-06066-8⟩, Nature Communications, Vol 9, Iss 1, Pp 1-11 (2018), Nature Communications, 2018, 9, pp.3704. ⟨10.1038/s41467-018-06066-8⟩
- Accession number :
- edsair.doi.dedup.....67f5e427615bf9141aad98cd7784b0cb