POLO-LIKE KINASE CDC5 REGULATES PERICENTROMERIC COHESIN PERSISTENCE
Embargo until
Date
2016-08-31
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Johns Hopkins University
Abstract
The high fidelity duplication and subsequent segregation of chromosomes is a requirement for life. An essential protein complex termed cohesin ensures that replicated sister chromatids properly segregate between the dividing cells. The DNA-tethering activity of this protein complex is regulated by a host of accessory factors, including the enigmatic polo-like kinase (Cdc5 in budding yeast). Evolutionarily conserved, polo-like kinases are thought to control the spatiotemporal regulation of cellular division programs by specific subcellular localization to, and phosphorylation of, their target proteins. In this dissertation I demonstrate that Cdc5 associates with chromosomes at centromeres, co-localizes with cohesin at centromeres and cohesin-associated regions (CARS), and physically interacts with the cohesin complex. Cdc5’s enrichment on chromosomes requires cohesin’s enrichment at the same loci. Intriguingly, both Cdc5 and cohesin’s enrichment at centromeres decrease when chromosomes are properly attached to the mitotic spindle. Finally, I have also generated a novel, auxin-sensitive allele of CDC5 (cdc5-aid), which may provide further insights into the interplay between cohesin and Cdc5: preliminary data suggests that depletion of cdc5-aid leads to cohesin persistence at centromeres, but not at chromosomal arm CARS, late in the cell cycle.
Description
Keywords
polo-like kinase, cohesin, chromosome segregation