Understanding the roles of the Smc5/6 complex on meiotic recombination

Kirk, Jacob Daniel (2017) Understanding the roles of the Smc5/6 complex on meiotic recombination. Doctoral thesis (PhD), University of Sussex.

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During meiotic cell division, the formation of chiasmata is required for the segregation of homologous chromosomes. This involves the formation of a programmed series of double strand breaks and repair by homologous recombination to form crossovers within the chromosomes. This process is highly regulated to ensure the timely formation of interhomolog linkages, which are normally repressed by the mitotic repair pathways. A protein complex of particular interest here is Smc5/6, which is closely related to two complexes with a fundamental role controlling chromosome structure (cohesin and condensin). In the absence of the Smc5/6 complex, cells are unable to separate their chromosomes efficiently during meiosis, resulting in a ‘cut phenotype’; this is thought to be due to major aberrations in the formation and resolution of joint molecule intermediates throughout meiotic prophase.

Here, I characterize the aberration in the formation of recombination intermediates in smc5/6-depleted cells in order to infer functions of the Smc5/6 complex in regulating recombination intermediates. Using the well-characterised DNA double strand break hotspot HIS4LEU2, I show that depletion of the Smc5/6 complex rescues joint molecule formation in a zmm repair pathway mutant. To understand the timing of Smc5/6 complex function during strand invasion, I analyse the genetic interactions between two recA orthologues and cohesin, all of which promote the orderly formation of recombination events between homologous chromosomes. Collectively, the findings suggest that the Smc5/6 complex stabilizes early recombination intermediates between homologous DNA substrates thereby imposing an interhomolog repair fate. I analyse the formation of repair intermediates in the absence of cohesin, and demonstrate that the role of the Smc5/6 complex in interhomolog repair bias is independent of the presence of cohesin, which is normally considered a fundamental factor in the establishment of repair bias.

Item Type: Thesis (Doctoral)
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics
Depositing User: Library Cataloguing
Date Deposited: 24 May 2017 08:31
Last Modified: 24 May 2017 08:31
URI: http://sro.sussex.ac.uk/id/eprint/68211

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