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

Arroyo, Maria ; Casas-Delucchi, Corella S. ; Pabba, Maruthi K. ; Prorok, Paulina ; Pradhan, Sunil K. ; Rausch, Cathia ; Lehmkuhl, Anne ; Maiser, Andreas ; Buschbeck, Marcus ; Pasque, Vincent ; Bernstein, Emily ; Luck, Katja ; Cardoso, M. Cristina (2024)
Histone variant macroH2A1 regulates synchronous firing of replication origins in the inactive X chromosome.
In: Nucleic acids research, 52 (9)
doi: 10.1093/nar/gkae734
Artikel, Bibliographie

Kurzbeschreibung (Abstract)

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.

Typ des Eintrags: Artikel
Erschienen: 2024
Autor(en): Arroyo, Maria ; Casas-Delucchi, Corella S. ; Pabba, Maruthi K. ; Prorok, Paulina ; Pradhan, Sunil K. ; Rausch, Cathia ; Lehmkuhl, Anne ; Maiser, Andreas ; Buschbeck, Marcus ; Pasque, Vincent ; Bernstein, Emily ; Luck, Katja ; Cardoso, M. Cristina
Art des Eintrags: Bibliographie
Titel: Histone variant macroH2A1 regulates synchronous firing of replication origins in the inactive X chromosome
Sprache: Englisch
Publikationsjahr: 27 August 2024
Verlag: Oxford University Press
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Nucleic acids research
Jahrgang/Volume einer Zeitschrift: 52
(Heft-)Nummer: 9
DOI: 10.1093/nar/gkae734
Kurzbeschreibung (Abstract):

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.

ID-Nummer: pmid:39189450
Zusätzliche Informationen:

Artikel-ID: gkae734

Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Cell Biology and Epigenetics
Hinterlegungsdatum: 02 Sep 2024 12:27
Letzte Änderung: 04 Nov 2024 13:07
PPN: 521060729
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