Date

2015

Document Type

Dissertation

Degree

Doctor of Philosophy

Department

Molecular Biology

First Adviser

Skibbens, Robert V.

Other advisers/committee members

Cassimeris, Lynne; Iovine, Mary K.; Dorsett, Dale

Abstract

All living organisms consist of cells that undergo a cell cycle to grow and divide so that the resulting daughter cells are exact replicas of the parent cell. To achieve this feat, a parent cell will first replicate its DNA into two identical copies during S phase of the cell cycle, and then segregate those copies into two daughter cells during anaphase of mitosis. Ensuring that daughter cells receive identical sets of chromosomes requires mechanisms that check for accurate DNA replication, compaction of replicated sister chromatids, and proper segregation of chromosomes. The protein complex termed cohesins identify replicated sister chromatids by tethering them together until anaphase. Additionally, cohesins function in proper chromosome condensation and DNA replication. Using the cohesion maintenance factor Pds5, a component of cohesins, this body of work explores the mechanisms of various cohesin-dependent pathways. These studies reveal that 1) sister chromatid coheison is mediated by a dimeric or oligomeric cohesin complex, 2) cohesin-dependent functions in sister chromatid cohesion and condensation are independently regulated, and 3) Pds5, in combination with Replication Factor C (Elg1-RFC), is required for DNA fork replication progression.

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