Diverse roles for histone H2A modifications in DNA damage response pathways in yeast

John D Moore1, Oya Yazgan, Yeganeh Ataian

  • 1Department of Biological Sciences, University of Alaska, Anchorage, Alaska 99508, USA.

Genetics
|October 10, 2006
PubMed

Insights

Histone H2A modifications in yeast are crucial for DNA repair pathways. Specific patterns of H2A tail modifications act as "damage codes" to direct repair processes for various DNA lesions.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • DNA damage is repaired by multiple pathways within the chromatin context.
  • Histone modifications play a role in DNA repair processes.

Purpose of the Study:

  • To investigate the role of histone H2A modifications in DNA repair pathways.
  • To identify specific H2A residues and their modifications involved in repair.

Main Methods:

  • Mutagenesis of modifiable residues in yeast H2A N- and C-terminal tails.
  • Assessing mutant strains in DNA repair assays (homologous recombination, nonhomologous end-joining, UV, oxidative damage).
  • Analyzing H2A phosphorylation patterns.

Main Results:

  • H2A tail residues are essential for double-strand break repair (homologous recombination and nonhomologous end-joining) and survival from UV/oxidative damage.
  • H2A serine 122 is critical for repair and survival across multiple assays.
  • Distinct patterns of H2A phosphorylation at S122, T126, and S129 were observed under different damage conditions.
  • Overlapping but non-identical H2A residue groups participate in different repair pathways.

Conclusions:

  • H2A tail modifications function as "damage codes" to signal specific DNA damage types.
  • These codes may direct the recruitment or activity of specific DNA repair pathways.
  • Histone H2A acts as a central regulator in the DNA damage response.

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