The Hsk1(Cdc7) Replication Kinase Regulates Origin Efficiency

• DOI: 10.1091/mbc.e08-06-0645
• Publication Date: 2008-09-18T00:53:59Z
• Authors: Prasanta K. Patel; Naveen Kommajosyula; Adam Rosebrock; Aaron Bensimon; Janet Leatherwood; John Bechhoefer; Nicholas Rhind
• Keywords: Pre-replication complex; Origin recognition complex; Replication timing; Replication

Origins of DNA replication are generally inefficient, with most firing in fewer than half cell cycles. However, neither the mechanism nor importance regulation origin efficiency is clear. In fission yeast, stochastic, leading us to hypothesize that inefficiency and stochasticity result a diffusible, rate-limiting activator. We show Hsk1-Dfp1 kinase (the yeast Cdc7-Dbf4 homologue) plays such role. Increasing or decreasing levels correspondingly increases decreases efficiency. Furthermore, tethering near an origin, suggesting effective local concentration regulates firing. Using photobleaching, we freely diffusible nucleus. These results support model which accessibility origins provides potential mechanistic link between chromatin structure timing. By manipulating levels, increasing rates leads increase genomic instability, demonstrating biological appropriate