DOI

10.17077/etd.0a6lzvn3

Document Type

Dissertation

Date of Degree

Spring 2018

Access Restrictions

Access restricted until 07/03/2020

Degree Name

PhD (Doctor of Philosophy)

Degree In

Biology

First Advisor

Sarit Smolikove

First Committee Member

Tina L. Tootle

Second Committee Member

Anna Malkova

Third Committee Member

Veena Prahlad

Fourth Committee Member

Robert E. Malone

Abstract

Meiosis is a specialized cellular division occurring in organisms capable of sexual reproduction that leads to the formation of gametes containing half of the original chromosome number. Meiosis involves two cell divisions, the first of which segregates homologous chromosomes to opposite poles, reducing ploidy by half. In most organisms, this segregation requires crossovers, the exchange of DNA sequences between homologous chromosomes, which in turn, is dependent upon stable associations of homologs. In early meiotic prophase I, chromosomes form pairing interactions that bring chromosomes into close physical associations. The process of synapsis then stabilizes these pairing interactions throughout the homolog pair, and is mediated by the synaptonemal complex (SC), a meiosis specific protein complex. Absent or misregulated assembly of the SC prevents the stabilization of pairing interactions that are essential for meiosis, leading to chromosome missegregation. Divided into two main projects, my work aimed to further our understanding of the regulation of synaptonemal complex assembly. One project examined meiotic chromosomal movement by characterizing a relatively unstudied protein in C. elegans, FKB-6. We showed that FKB-6 is important for creating pauses between chromosome movements. These pauses are needed for allowing chromosomes to properly pair and thus allowing for proper SC assembly. In the absence of FKB-6, a decrease in pausing occurs which perturbs chromosome pairing and causes SC assembly defects. A second project examined the role of CUL-4, an E3 ubiquitin ligase, in meiotic prophase I. We show that CUL-4 plays a role in both SC assembly and meiotic recombination. This work exemplifies the multiple levels of control of SC assembly which still require further study.

Keywords

C. elegans, CUL-4, FKB-6, Meiosis, Synaptonemal Complex

Pages

xiii, 235 pages

Bibliography

Includes bibliographical references.

Copyright

Copyright © 2018 Benjamin Alleva

Available for download on Friday, July 03, 2020

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