Date

2018

Document Type

Dissertation

Degree

Doctor of Philosophy

Department

Molecular Biology

First Adviser

Skibbens, Robert V.

Abstract

During interphase, chromatin is in a state of least condensation and most accessible to transcription factors. When cells enter mitosis, replicated chromosomes are compacted, and sister chromatids are cohered to form specific mitotic architectures, which are essential for appropriate chromosome segregation. Disruption of the formation, regulation and maintenance of mitotic chromosome structure results in aneuploidy, which is tightly correlated with severe developmental maladies, aging and tumorigenesis. To understand how cells achieve mitotic condensed DNA architectures, we focus on the regulation of helicase activity and also the impact of site-specific condensation events. We report that helicase the Chl1 acts a novel regulator of mitotic chromosome condensation through cohesin-based mechanisms, revealing an exciting interface between native DNA structure that relies on helicase activity and higher-ordered chromosome compaction that requires cohesin complex. We also report for the first time that the condensed rDNA locus retains great plasticity during mitosis and responds to elevated temperature through a novel hypercondensation activity. This hyperthermic-induced rDNA hypercondensation is based on heat shock chaperone Hsp82, revealing a new role for chaperones in regulating mitotic DNA architecture.

Share

COinS