title: The histone variant H2A.Bbd is enriched at sites of DNA synthesis.
abstract: Histone variants play an important role in shaping the mammalian epigenome and their aberrant expression is frequently observed in several types of cancer. However, the mechanisms that mediate their function and the composition of the variant-containing chromatin are still largely unknown. A proteomic interrogation of chromatin containing the different H2A variants macroH2A.1.2, H2A.Bbd and H2A revealed a strikingly different protein composition. Gene ontology analysis reveals a strong enrichment of splicing factors as well as components of the mammalian replisome in H2A.Bbd-containing chromatin. We find H2A.Bbd localizing transiently to sites of DNA synthesis during S-phase and during DNA repair. Cells that express H2A.Bbd have a shortened S-phase and are more susceptible to DNA damage, two phenotypes that are also observed in human Hodgkin's lymphoma cells that aberrantly express this variant. Based on our experiments we conclude that H2A.Bbd is targeted to newly synthesized DNA during replication and DNA repair. The transient incorporation of H2A.Bbd may be due to the intrinsic instability of nucleosomes carrying this variant or a faster chromatin loading. This potentially leads to a disturbance of the existing chromatin structure, which may have effects on cell cycle regulation and DNA damage sensitivity.
authors.affiliation: Munich Center of Integrated Protein Science, Ludwig Maximilians University of Munich, 80336 Munich, Germany.
authors.forename: Viola
authors.initials: V
authors.lastname: Sansoni
authors.affiliation: Technische Universität Darmstadt Schnittspahnstr. 10, 64287 Darmstadt, Germany.
authors.forename: Corella S
authors.initials: CS
authors.lastname: Casas-Delucchi
authors.affiliation: Technische Universität Darmstadt Schnittspahnstr. 10, 64287 Darmstadt, Germany.
authors.forename: Malini
authors.initials: M
authors.lastname: Rajan
authors.affiliation: Munich Center of Integrated Protein Science, Ludwig Maximilians University of Munich, 80336 Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Adolf-Butenandt Institute, Ludwig Maximilians University of Munich, 80336 Munich, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Bönisch
authors.affiliation: Munich Center of Integrated Protein Science, Ludwig Maximilians University of Munich, 80336 Munich, Germany.
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Thomae
authors.affiliation: Department of Pediatrics, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06097 Halle, Germany.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Staege
authors.affiliation: Munich Center of Integrated Protein Science, Ludwig Maximilians University of Munich, 80336 Munich, Germany Adolf-Butenandt Institute, Ludwig Maximilians University of Munich, 80336 Munich, Germany.
authors.forename: Sandra B
authors.initials: SB
authors.lastname: Hake
authors.affiliation: Technische Universität Darmstadt Schnittspahnstr. 10, 64287 Darmstadt, Germany.
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Cardoso
authors.affiliation: Munich Center of Integrated Protein Science, Ludwig Maximilians University of Munich, 80336 Munich, Germany Adolf-Butenandt Institute, Ludwig Maximilians University of Munich, 80336 Munich, Germany Imhof@lmu.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Imhof
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002843:Chromatin / Q000737:chemistry; D004247:DNA / Q000096:biosynthesis*; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D005260:Female; D014644:Genetic Variation; D006657:Histones / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice
chemical_list: D002843:Chromatin; D006657:Histones; D004247:DNA
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