{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Shoaib M"],"funding":["Cancer Research UK","Wellcome Trust"],"pagination":["3704"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6135857"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(1)"],"pubmed_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."],"journal":["Nature communications"],"pubmed_title":["Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing."],"pmcid":["PMC6135857"],"funding_grant_id":["14301","097945/C/11/Z","096598/Z/11/Z"],"pubmed_authors":["Fahrenkrog B","Lerdrup M","Walter D","Julien E","Shoaib M","Lleres D","Blow JJ","Hansen K","Sorensen CS","Gillespie PJ","Izard F","Johansen JV"],"additional_accession":[]},"is_claimable":false,"name":"Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing.","description":"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.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Sep","modification":"2026-05-05T23:16:17.129Z","creation":"2019-03-26T23:55:52Z"},"accession":"S-EPMC6135857","cross_references":{"pubmed":["30209253"],"doi":["10.1038/s41467-018-06066-8"]}}