Histone H3K79 methylation has been shown to play roles in different DNA repair pathways. Histone H4 residues serine 64 to threonine 80 surround histone H3K79 residue. We have analyzed the effect of the mutations of the residues on UV sensitivity, H3K79 methylation, nucleotide excision repair, chromatin state and homologous recombination. We found that mutation of the residues 64 to 72 cause resistance to killing by UV whereas mutation of the residues 73 to 80 cause sensitivity to killing by UV compared to wild type. In general, we found that the mutations make nucleotide excision repair more proficient at the constitutively active RPB2 loci. We found global genomic repair is faster in most of the mutants except H75E. Transcription coupled repair is normal in most of the mutants except mutant Y72T. In mutant H75E, Rad26 independent transcription coupled repair is also defective. The mutations T73D, T73F and T73Y affect mono, di and tri methylation of H3K79 but they have faster or normal nucleotide excision repair. We have also found that these histone mutations make chromatin more accessible to micrococcal nuclease. The UV sensitive histone mutants have normal or faster nucleotide excision repair. Methyl methane sulfonate (MMS) sensitivity test, Rad14 and Rad52 epistasis analysis suggests that the UV sensitive histone H4 mutants could play role in homologous recombination repair pathway. Taken together, the results imply that the histone mutations remodel the chromatin that helps to recruit nucleotide excision repair factors for efficient repair.
| Identifer | oai:union.ndltd.org:LSU/oai:etd.lsu.edu:etd-07112016-153156 |
| Date | 29 July 2016 |
| Creators | Rahman, Sheikh Arafatur |
| Contributors | Li, Shisheng, Yoshimura, Masami, Cheng, Henrique |
| Publisher | LSU |
| Source Sets | Louisiana State University |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lsu.edu/docs/available/etd-07112016-153156/ |
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