Regulation of Chromosome Segregation by Replication Proteins

University Of Southern California, Los Angeles CA

Investigators

Abstract

Faithful chromosome segregation is essential to the life of a eukaryotic cell. This project will characterize novel connections between DNA replication and chromosome segregation, using fission yeast as a model eukaryotic system. It suggests that proteins involved in the initiation of DNA replication may have linked functions in assembling active centromeres and segregation-competent chromosomes during each cell cycle. This analysis builds on prior work suggesting that replication proteins affect several stages of centromere function, including heterochromatin assembly at the centromere, chromosome condensation, and regulation of centromere attachment. The proposal hypothesizes that DNA replication proteins are required to remodel various components of centromere function during each cell cycle. The first aim analyzes physical interactions between replication proteins and the heterochromatin protein HP1/Swi6. The second aim investigates whether Swi6 influences assembly or activation of replication complexes and replication timing in the centromere region. The final aim screens for additional mutants that define genes that link replication and chromosome segregation. The ultimate goal is to understand the network linking these events. This project investigates a fundamental question of cell division by investigating how the events of DNA replication affect accurate chromosome segregation in all eukaryotic cells. Its ultimate goal is to identify a genetic network that regulates these process that can be used as a framework for more mechanistic studies in the future. It will promote teaching, training, and learning by actively involving PhD students and undergraduates in carrying out the research, ensuring an educational impact in addition to scientific advancement.