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Originally published as Genetics Published Articles Ahead of Print on October 8, 2006.

Genetics, Vol. 176, 15-25, May 2007, Copyright © 2007
doi:10.1534/genetics.106.063792

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Diverse Roles for Histone H2A Modifications in DNA Damage Response Pathways in Yeast

John D. Moore, Oya Yazgan, Yeganeh Ataian and Jocelyn E. Krebs1

Department of Biological Sciences, University of Alaska, Anchorage, Alaska 99508

1 Corresponding author: Department of Biological Sciences, 3211 Providence Dr., University of Alaska, Anchorage, AK 99508.
E-mail: afjek{at}uaa.alaska.edu

There are many types of DNA damage that are repaired by a multiplicity of different repair pathways. All damage and repair occur in the context of chromatin, and histone modifications are involved in many repair processes. We have analyzed the roles of H2A and its modifications in repair by mutagenizing modifiable residues in the N- and C-terminal tails of yeast H2A and by testing strains containing these mutations in multiple DNA repair assays. We show that residues in both tails are important for homologous recombination and nonhomologous end-joining pathways of double-strand break repair, as well as for survival of UV irradiation and oxidative damage. We show that H2A serine 122 is important for repair and/or survival in each of these assays. We also observe a complex pattern of H2A phosphorylation at residues S122, T126, and S129 in response to different damage conditions. We find that overlapping but nonidentical groups of H2A residues in both tails are involved in different pathways of repair. These data suggest the presence of a set of H2A "damage codes" in which distinct patterns of modifications on both tails of H2A may be used to identify specific types of damage or to promote specific repair pathways.




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Mol. Cell. Biol.Home page
M. Fink, D. Imholz, and F. Thoma
Contribution of the Serine 129 of Histone H2A to Chromatin Structure
Mol. Cell. Biol., May 15, 2007; 27(10): 3589 - 3600.
[Abstract] [Full Text] [PDF]




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