Characterisation of the histone H2A C-terminal tail in DNA damage responses in S. cerevisiae

• Main Author: Harvey, A. C.
• Published: University of Cambridge 2005
• Subjects: 572.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603822

Within the eukaryotic nucleus DNA is compacted into chromatin, the smallest unit of which is the nucleosome. Nuclear processes that require direct access to DNA such as transcription, replication and repair must therefore operate in a chromatin context/ It is recently become apparent that proteins that contribute to chromatin structure and its modulation are of integral importance in these essential pathways. Many studies have shown the importance of covalent modifications of histone proteins in regulating chromatin structure and in protein recruitment. Such modifications can include phosphorylation, acetylation, methylation and ubiquitination. It has previously been demonstrated that the phosphorylation of serine 129 (S129) in the C-terminal tail of budding yeast histone H2A is important for DNA double-strand break responses. Here, we take a systematic site-directed mutagenesis approach to determine the importance of other modifiable residues in the H2A C-terminal tail. We identify another histone H2A serine residue (S122) that is also important for cell survival in the presence of DNA damaging agents. We have characterized yeast strains lacking this residue and find that this residue does not significantly affect the ability of cells to detect or signal the presence of DNA damage. In contrast, these strains are growth deficient, sporulation defective and impaired in DNA double-strand break repair. Moreover, we shown that H2A S122 and H2A S129 are functioning distinctly in DNA damage responses. We also further characterize the role of H2A S129 phosphorylation in DNA damage and cellular stress responses. Finally, it has previously been shown that the yeast linker histone plays a role in mediating DNA DSB repair, and the relationship with the H2A C-terminal tail was examined.