MCM2 promotes symmetric inheritance of modified histones during DNA replication

Nataliya Petryk; Maria Dalby; Alice Wenger; Caroline B. Stromme; Anne Strandsby; Robin Andersson; Anja Groth

doi:10.1126/science.aau0294

MCM2 promotes symmetric inheritance of modified histones during DNA replication

Nataliya Petryk, Maria Dalby, Alice Wenger, Caroline B. Stromme, Anne Strandsby, Robin Andersson, Anja Groth

66 Citations (Scopus)

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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 arkedly 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.

Original language	English
Journal	Science
Volume	361
Issue number	6409
Pages (from-to)	1389-1392
Number of pages	3
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.aau0294
Publication status	Published - 28 Sept 2018

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title = "MCM2 promotes symmetric inheritance of modified histones during DNA replication",

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 arkedly 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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T1 - MCM2 promotes symmetric inheritance of modified histones during DNA replication

AU - Petryk, Nataliya

AU - Dalby, Maria

AU - Wenger, Alice

AU - Stromme, Caroline B.

AU - Strandsby, Anne

AU - Andersson, Robin

AU - Groth, Anja

PY - 2018/9/28

Y1 - 2018/9/28

N2 - 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 arkedly 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.

AB - 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 arkedly 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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MCM2 promotes symmetric inheritance of modified histones during DNA replication

Abstract

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