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Science. 2018 Sep 28;361(6409):1389-1392. doi: 10.1126/science.aau0294. Epub 2018 Aug 16.

MCM2 promotes symmetric inheritance of modified histones during DNA replication.

Author information

1
Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
2
Novo Nordisk Foundation Center for Protein Research (CPR), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
3
The Bioinformatics Centre, Department of Biology, Faculty of Science, University of Copenhagen, 2200 Copenhagen, Denmark.
4
The Bioinformatics Centre, Department of Biology, Faculty of Science, University of Copenhagen, 2200 Copenhagen, Denmark. robin@binf.ku.dk anja.groth@bric.ku.dk.
5
Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. robin@binf.ku.dk anja.groth@bric.ku.dk.

Abstract

During genome replication, parental histones are recycled to newly replicated DNA with their posttranslational modifications (PTMs). Whether sister chromatids inherit modified histones evenly remains unknown. We measured histone PTM partition to sister chromatids in embryonic stem cells. We found that parental histones H3-H4 segregate to both daughter DNA strands with a weak leading-strand bias, skewing partition at topologically associating domain (TAD) borders and enhancers proximal to replication initiation zones. Segregation of parental histones to the leading strand increased markedly in cells with histone-binding mutations in MCM2, part of the replicative helicase, exacerbating histone PTM sister chromatid asymmetry. This work reveals how histones are inherited to sister chromatids and identifies a mechanism by which the replication machinery ensures symmetric cell division.

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PMID:
30115746
DOI:
10.1126/science.aau0294
[Indexed for MEDLINE]

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