Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing
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Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing. / Shoaib, Muhammad; Walter, David; Gillespie, Peter J.; Izard, Fanny; Fahrenkrog, Birthe; Lleres, David; Lerdrup, Mads; Johansen, Jens Vilstrup; Hansen, Klaus; Julien, Eric; Blow, J. Julian; Sørensen, Claus S.
I: Nature Communications, Bind 9, Nr. 1, 3704, 2018, s. 1-11.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing
AU - Shoaib, Muhammad
AU - Walter, David
AU - Gillespie, Peter J.
AU - Izard, Fanny
AU - Fahrenkrog, Birthe
AU - Lleres, David
AU - Lerdrup, Mads
AU - Johansen, Jens Vilstrup
AU - Hansen, Klaus
AU - Julien, Eric
AU - Blow, J. Julian
AU - Sørensen, Claus S.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-018-06066-8
DO - 10.1038/s41467-018-06066-8
M3 - Journal article
C2 - 30209253
AN - SCOPUS:85053243728
VL - 9
SP - 1
EP - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3704
ER -
ID: 203592453