Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing

• DOI: 10.1038/s41467-018-06066-8
• Publication Date: 2018-09-06T14:04:47Z
• Authors: Muhammad Shoaib; David Walter; Peter J. Gillespie; Fanny Izard; Birthe Fahrenkrog; David Lleres; Mads Lerdrup; Jens Vilstrup Joh...; Klaus Hansen; Eric Julien; J. Julian Blow; Claus S. Sørensen
• Keywords: DNA re-replication; Histone code

The decompaction and re-establishment of chromatin organization immediately after mitosis is essential for genome regulation. Mechanisms underlying structure control in daughter cells are not fully understood. Here we show that a compaction threshold exiting ensures integrity by limiting replication licensing G1 phase. Upon mitotic exit, relaxation controlled SET8-dependent methylation histone H4 on lysine 20. In the absence either SET8 or H4K20 residue, substantial genome-wide occurs allowing excessive loading origin recognition complex (ORC) cells. ORC overloading stimulates aberrant recruitment MCM2-7 promotes single-stranded DNA formation damage. Restoring restrains excess loss integrity. Our findings identify cell cycle-specific mechanism whereby fine-tuned suppresses detrimental maintains at cellular transition from to