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Title: The role of H2B in double-strand break repair in S. cerevisiae
Author: Foster, E. R.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2008
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Histone modifications can act as signals, providing binding surfaces for proteins involved in DNA repair, and chromatin remodellers which disrupt histone-DNA interactions, which can make the DNA more accessible. Recent studies have shed light on the roles of some histone residues that function specifically in response to DNA repair, such as H2A S129, which is phosphorylated after DNA damage. However it seems clear that there are many more histone residues with roles in DNA damage responses that remain to be elucidated. This work examines the roles of three residues located at the C terminus of histone H2B; K123, S125, and S126. When all three residues are altered, the cell is unable to survive efficiently in the presence of DNA damage. Characterisation of a strain with alterations in these residues has shown that the pathway responsible for H2B ubiquitination has a role in the repair of double strand breaks, particularly in homologous recombination. Further studies showed that the role of histone H2B in DNA repair is distinct from that of histone H2A S129. Genetic interactions were noted between H2B and the DNA repair protein Mus81, and the yeast linker histone Hhol. It has previously been demonstrated that modification of K123 by ubiquitination influences methylation of histone H3. This relationship was explored further, and an unexpected role for serines S125 and S126 in regulating the status of H3 methylation was uncovered. Related to this, a previously uncharacterised methylation site on H3 (K64) was examined in order to determine whether it functions in the cellular response to DNA damage. Histone H2B ubiquitination is known to exist in human cells, and as DNA repair pathways are highly conserved between yeast and mammals it seems likely that H2B plays an important role in DNA repair in higher eukaryotic organisms.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available