February 19, 2015
- Susan Forsburg, Ph.D.
- Biological Sciences
Understanding Hsk1’s Multifaceted Role in Maintaining Genome Integrity in Fission Yeast through Identifying Proteins that Interact with the Hsk1/Dfp1 Complex
Cell Division Cycle 7 (CDC7), a gene conserved in eukaryotes, encodes for the protein Cdc7. The fission yeast Cdc7 kinase homologue is the Hsk1 (homologue of Cdc7 (seven) kinase 1) complex, which is composed of a catalytic subunit, Hsk1p, and a regulatory subunit, Dfp1 (dbf4 four in pombe). Binding of Dfp1 to Hsk1 gives specificity to Hsk1’s functions by causing it to phosphorylate critical substrates. Hsk1 plays a crucial role in DNA replication, S-phase checkpoint control, cellular recovery from DNA damage, centromere cohesion, meiotic recombination, and formation of meiotic dsDNA breaks. However, most of Hsk1’s functions during cell division still remain unknown; this project continued to characterize the functions and activities of Hsk1 in fission yeast by identifying novel proteins that interact with both Hsk1 and Dpf1. The project used fission yeast, Schizosaccharomyces pombe, since it is a simple model system whose genome has been completely sequenced. Two-hybrid screening was used to identify proteins that interact with Hsk1 and Dfp1 during mitosis and meiosis, respectively, and DNA sequencing of the proteins helped us to determine whether they had been previously identified. The results from this project ultimately helped shed light on Hsk1’s various roles in maintaining genome integrity during cell division. This is significant since understanding more about the genes and proteins involved in cell division in yeast will allow us to learn more about the control of cell division in humans and the relationship between genome stability and cancer.