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      Histone H2A variants: Diversifying chromatin to ensure genome integrity.

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          Abstract

          Histone variants represent chromatin components that diversify the structure and function of the genome. The variants of H2A, primarily H2A.X, H2A.Z and macroH2A, are well-established participants in DNA damage response (DDR) pathways, which function to protect the integrity of the genome. Through their deposition, post-translational modifications and unique protein interaction networks, these variants guard DNA from endogenous threats including replication stress and genome fragility as well as from DNA lesions inflicted by exogenous sources. A growing body of work is now providing a clearer picture on the involvement and mechanistic basis of H2A variant contribution to genome integrity. Beyond their well-documented role in gene regulation, we review here how histone H2A variants promote genome stability and how alterations in these pathways contribute to human diseases including cancer.

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          Author and article information

          Journal
          Semin Cell Dev Biol
          Seminars in cell & developmental biology
          Elsevier BV
          1096-3634
          1084-9521
          Mar 21 2022
          Affiliations
          [1 ] Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287 USA. Electronic address: PO@jhmi.edu.
          [2 ] Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA; Livestrong Cancer Institutes, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: kyle.miller@austin.utexas.edu.
          Article
          S1084-9521(22)00078-7 NIHMS1791488
          10.1016/j.semcdb.2022.03.011
          9489817
          35331626
          abcf38fc-d306-4ddb-94b0-5670930d45c9
          Copyright © 2022 Elsevier Ltd. All rights reserved.
          History

          DNA repair,Genome integrity,H2A variants,H2AX,Histones,MacroH2A
          DNA repair, Genome integrity, H2A variants, H2AX, Histones, MacroH2A

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