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Title: The identification of a meiosis-specific phosphorylation of exonuclease-I during the meiotic recombination pathway in Saccharomyces cerevisiae
Author: Alnaser, Hasan F. H.
ISNI:       0000 0004 8509 2863
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2019
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Meiosis is a cell division process specialised for the production of four genetically distinct haploid daughter cells from a single diploid parent cell. A meiosis-specific process of homologous recombination repairs Spo11 induced DNA double-strand breaks (DSBs) creating gene conversions and crossovers; a crucial pathway for genetic diversity and homologous chromosomes disjunction. An important step in this process is the resection of DSB sites to expose 3’ single-stranded overhangs, which can then proceed to search for its homologous repair template. Exonuclease-1(Exo1) is a conserved nuclease with 5’ → 3’ DNA exonuclease activity and 5’ flap endonuclease activity. Exo1 is required for progressive resection necessary for long tracts of 3’ single-stranded DNA, critical for normal levels of recombination. The phosphorylation of Exo1 was first observed in response to DNA damage in Saccharomyces cerevisiae and this negatively regulates Exo1 nuclease activity. In this study, the phosphorylation of Exo1 during meiosis was investigated. After analysing Exo1 meiotic-phosphorylation by mass-spectrometry, additional residues were found to be phosphorylated in comparison to mitotically significant residues. The meiotic phosphorylation of Exo1 was found to be Tel1-dependent, and MRX complex dependent. Phosphorylated Exo1 may function during the bidirectional resection of Spo11 induced DSBs, and function of this phosphorylation event is yet to be characterised.
Supervisor: Hu, Bin ; Goldman, Alastair Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available