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A negatively charged residue in place of histone H3K56 supports chromatin assembly factor association but not genotoxic stress resistance.

DNA repair | Dec 3, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19796999

In fungal species, lysine 56 of newly synthesized histone H3 molecules is modified by the acetyltransferase Rtt109, which promotes resistance to genotoxic agents. To further explore how H3 K56ac contributes to genome stability, we conducted screens for suppressors of the DNA damage sensitivity of budding yeast rtt109 Delta mutants. We recovered a single extragenic suppressor mutation that efficiently restored damage resistance. The suppressor is a point mutation in the histone H3 gene HHT2, and converts lysine 56 to glutamic acid. In some ways, K56E mimics K56ac, because it suppresses other mutations that interfere with the production of H3 K56ac and restores histone binding to chromatin assembly proteins CAF-1 and Rtt106. Therefore, we demonstrate that enhanced association with chromatin assembly factors can be accomplished not only by acetylation-mediated charge neutralization of H3K56 but also by the replacement of the positively charged lysine with an acidic residue. These data suggest that removal of the positive charge on lysine 56 is the functionally important consequence of H3K56 acetylation. Additionally, the suppressive function of K56E requires the presence of a second H3 allele, because K56E impairs growth when it is the sole source of histones, even more so than does constitutive H3K56 acetylation. Our studies therefore emphasize how H3 K56ac not only promotes chromatin assembly but also leads to chromosomal malfunction if not removed following histone deposition.

Pubmed ID: 19796999 RIS Download

Mesh terms: Alleles | Chromatin Assembly and Disassembly | DNA Damage | Gene Expression Regulation, Fungal | Histone Acetyltransferases | Histones | Mutation | Phenotype | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins

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Associated grants

  • Agency: NIGMS NIH HHS, Id: 1 F32 GM075601-01
  • Agency: NIGMS NIH HHS, Id: R01 GM055712
  • Agency: NIGMS NIH HHS, Id: R01 GM055712-12
  • Agency: NIGMS NIH HHS, Id: R01 GM55712

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