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Histone variant macroH2A1 regulates synchronous firing of replication origins in the inactive X chromosome

dc.contributor.author Arroyo-Lopez, Maria C
dc.contributor.author Casas-Delucchi, Corella S.
dc.contributor.author Pabba, Maruthi K.
dc.contributor.author Prorok, Paulina
dc.contributor.author Pradhan, Sunil K.
dc.contributor.author Rausch, Cathia
dc.contributor.author Lehmkuhl, Anne
dc.contributor.author Maiser, Andreas
dc.contributor.author Buschbeck, Marcus
dc.contributor.author Pasque, Vincent
dc.contributor.author Bernstein, Emily
dc.contributor.author Luck, Katja
dc.contributor.author Cardoso, M. Cristina
dc.date.accessioned 2024-07-03T15:10:44Z
dc.date.available 2024-02-02T10:09:59Z
dc.date.available 2024-07-03T15:10:44Z
dc.date.created 2024-07
dc.date.issued 2024-07-03
dc.description MacroH2A has been linked to transcriptional silencing, cell identity, and is a hallmark of the inactive X chromosome (Xi). However, it remains unclear whether macroH2A plays a role in DNA replication. Using knockdown/knockout cells for each macroH2A isoform, we show that macroH2A-containing nucleosomes slow down replication progression rate in the Xi reflecting the higher nucleosome stability. Moreover, macroH2A1, but not macroH2A2, regulates the number of nano replication foci in the Xi, and macroH2A1 downregulation increases DNA loop sizes corresponding to replicons. This relates to macroH2A1 regulating replicative helicase loading during G1 by interacting with it. We mapped this interaction to a phenylalanine in macroH2A1 that is not conserved in macroH2A2 and the C-terminus of Mcm3 helicase subunit. We propose that macroH2A1 enhances the licensing of pre-replication complexes via DNA helicase interaction and loading onto the Xi. de_DE
dc.description.version For publication de_DE
dc.identifier.uri https://tudatalib.ulb.tu-darmstadt.de/handle/tudatalib/4126.2
dc.identifier.uri https://doi.org/10.48328/tudatalib-1344.2
dc.language.iso en de_DE
dc.rights.licenseCC-BY-NC-4.0 (https://creativecommons.org/licenses/by-nc/4.0)
dc.subject Histone variants de_DE
dc.subject macroH2A de_DE
dc.subject inactive X de_DE
dc.subject origins de_DE
dc.subject replication de_DE
dc.subject replication synchrony de_DE
dc.subject.classification 2.11-03
dc.subject.ddc 570
dc.title Histone variant macroH2A1 regulates synchronous firing of replication origins in the inactive X chromosome de_DE
dc.type Dataset de_DE
dc.type Text de_DE
dc.type Image de_DE
dc.type Audiovisual de_DE
dcterms.accessRights openAccess
person.identifier.orcid 0000-0002-5837-8060
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person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
tuda.history.classification Version=2020-2024;201-03 Zellbiologie
tuda.unit TUDa

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