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Title: The roles of SCC-2 during C. elegans meiosis
Author: Lightfoot, James William
ISNI:       0000 0004 2721 3620
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2011
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Cohesin mediates sister chromatid cohesion (SCC), and its regulated association with chromatin is required to promote faithful chromosome segregation during mitosis and meiosis, as well as for the efficient repair of DNA double strand breaks (DSBs). In the mitotic cell cycle loading of cohesin requires a conserved complex containing the Scc2INipbl protein, which has also been proposed to promote binding of the cohesin-related complexes condensin and SMC-5/6. However, little is known about the factors that promote loading of cohesin and related SMC (structural maintenance of chromosomes) complexes during meiosis. During a screen for meiotic mutants in C. elegans, I isolated an allele of sec- 2, scc-2 (jql), that has allowed me to determine the roles that SCC-2 plays during meiosis. I show that during C. elegans meiosis loading of cohesin, but not condensin 11 or SMC-5/6, requires SCC-2, demonstrating that loading of condensin 11 and SMC-5/6 can be achieved by mechanisms independent of both SCC-2 and cohesin. The lack of cohesin in scc-2 mutants impairs the repair of meiotic DSBs and recombination intermediates accumulate extensively. Surprisingly, these accumulated intermediates fail to induce an apoptotic response, which is the normal outcome when persistent DNA lesions are detected by the conserved pachytene DNA damage checkpoint. I observed that this defect is caused by a failure to load the DNA damage sensor 9-1 ~ I complex onto persistent recombination intermediates in scc-2 mutants. A lack of meiotic cohesin also impairs the timely loading of the RAD-51 recombinase to irradiation-induced DSBs. These findings suggest that meiotic cohesin is required in the early steps of DSB processing and for the recruitment of checkpoint proteins to sites of DNA damage, thus revealing novel roles for cohesin.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available