2. Academic Validation
  3. The histone variant H2A.Bbd is enriched at sites of DNA synthesis

The histone variant H2A.Bbd is enriched at sites of DNA synthesis

  • Nucleic Acids Res. 2014 Jun;42(10):6405-20. doi: 10.1093/nar/gku303.
Viola Sansoni 1,  Corella S Casas-Delucchi 2,  Malini Rajan 2,  Andreas Schmidt 1,  Clemens Bönisch 3,  Andreas W Thomae 1,  Martin S Staege 4,  Sandra B Hake 5,  M Cristina Cardoso 2,  Axel Imhof 6
Affiliations

Affiliations

  • 1 Munich Center of Integrated Protein Science, Ludwig Maximilians University of Munich, 80336 Munich, Germany.
  • 2 Technische Universität Darmstadt Schnittspahnstr. 10, 64287 Darmstadt, Germany.
  • 3 Adolf-Butenandt Institute, Ludwig Maximilians University of Munich, 80336 Munich, Germany.
  • 4 Department of Pediatrics, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06097 Halle, Germany.
  • 5 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.
  • 6 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 [email protected].
PMID: 24753410 DOI: 10.1093/nar/gku303
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.

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