RT Journal Article SR Electronic T1 A histone H4K20 methylation-mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing JF bioRxiv FD Cold Spring Harbor Laboratory SP 350033 DO 10.1101/350033 A1 Muhammad Shoaib A1 David Walter A1 Peter J. Gillespie A1 Fanny Izard A1 Birthe Fahrenkrog A1 David Lleres A1 Mads Lerdrup A1 Jens Vilstrup Johansen A1 Klaus Hansen A1 Eric Julien A1 J. Julian Blow A1 Claus S. Sørensen YR 2018 UL http://biorxiv.org/content/early/2018/06/27/350033.abstract AB The decompaction and re-establishment of chromatin organization immediately after mitosis is essential for genome regulation. The 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, appropriate chromatin relaxation is safeguarded by SET8-dependent methylation of histone H4 on lysine 20. Thus, in the absence of either SET8 or the H4K20 residue, substantial genome-wide chromatin decompaction occurs which allows 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 the 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.