Date of Award

2013

Degree Type

Thesis

Department

Biological, Geological and Environmental Sciences

First Advisor

Boerner, Valentin

Subject Headings

Yeast, Meiosis, DNA -- Research, Biology Cellular Biology

Abstract

During meiosis, one round of DNA replication is followed by two rounds of chromosome segregation, producing four haploid gametes from each diploid precursor cell. Self-inflicted DNA double-strand breaks (DSBs) occur in prophase of meiosis I. A subset of DSBs are repaired using the homologous chromosome as template for homologous recombination, generating crossovers/chiasmata. When processing of DSBs is defective, the recombination checkpoint delays onset of the first meiotic cell division. Here, I have investigated mechanisms by which the budding yeast S. cerevisiae responds to low levels of initiating DSBs. A novel checkpoint is identified that is specifically triggered by low DSB levels, but not a lack thereof. This checkpoint is mediated by widely-conserved meiotic checkpoint ATPase Pch2. I propose that during normal meiosis, this low DSB checkpoint delays progress through meiosis until threshold levels of DSBs have been reached. Using genetic approaches, I have also identified three pathways by which the viability of gametes formed during low-DSB meiosis can be improved. Accordingly, (i) higher temperatures, (ii) abrogation of DSB-dependent histone H2A phosphorylation and (iii) overexpression of chromosome structure protein Hop1 constitute determinants for functional gamete formation at low DSB levels. Together, these findings suggest the existence of several layers that ensure faithful chromosome segregation during meiosis

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