SEARCH
ENGLISH
Histone acetylation has been shown to play an important role in DNA repair, including repair of double-strand breaks. Mutations that affect cell acetylation are sensitive to DNA damaging agents, either by mutating the catalytic unit of NuA4, that is the HAT that acetylates histone H4, or by acetylating lysine residues on the N-terminal tail of histone H4. Beside, our data show that wild-type yeast cells become equally sensitive to IR in the presence of histone acetylase (HAT) inhibitors. However, the details of the mechanism are unclear.
The goal of this project is to study the mechanism by which HAT inhibition can sensitize cells in yeast cells to IR. We believe that acetylation of the DSB-flanking histone h4 peptide is critical for the recruitment of specific DNA repair genes that initiate repair. We plan to identify those repair genes. The experimental design is based on global epistasis analysis using a library of 4700 single deletion yeast strains. When this pool was treated with a HAT inhibitor, functional double mutants were generated. We will identify those mutants that do not change IR sensitivity after treatment with HAT inhibitors. We hypothesized that the genes deleted in these mutants are repair proteins and that they are part of the repair pathway mediated by histone acetylation. We will then further characterize these gene protein products by finding out whether they interact directly with histones or whether they localize to DNA repair foci.
When this pool was treated with a HAT inhibitor, functional double mutants were generated. We will identify those mutants that do not change IR sensitivity after treatment with HAT inhibitors. We hypothesized that the genes deleted in these mutants are repair proteins and that they are part of the repair pathway mediated by histone acetylation. We will then further characterize these gene protein products by finding out whether they interact directly with histones or whether they localize to DNA repair foci. When this pool was treated with a HAT inhibitor, functional double mutants were generated. We will identify those mutants that do not change IR sensitivity after treatment with HAT inhibitors. We hypothesized that the genes deleted in these mutants are repair proteins and that they are part of the repair pathway mediated by histone acetylation. We will then further characterize these gene protein products by finding out whether they interact directly with histones or whether they localize to DNA repair foci.
English 
