期刊
GENES & DEVELOPMENT
卷 18, 期 9, 页码 981-991出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1202304
关键词
cell cycle control; DNA replication; cyclin-dependent kinase; origin recognition complex; genomic stability; re-replication
资金
- NIGMS NIH HHS [GM 052339, R01 GM052339, GM 047238, R01 GM047238] Funding Source: Medline
Cyclin-dependent kinases are critical regulators of eukaryotic DNA replication. We show that the S-phase cyclin Clb5 binds stably and directly to the origin recognition complex (ORC). This interaction is mediated by an RXL target sequence, or Cy motif, in the Orc6 subunit that is recognized by the hydrophobic patch region on Clb5. The Clb5-Orc6 interaction requires replication initiation, and is maintained throughout the remainder of S phase and into M phase. Eliminating the Clb5-Orc6 interaction has no effect on initiation of replication but instead sensitizes cells to lethal overreplication. We propose that Clb5 binding to ORC provides an origin-localized replication control switch that specifically prevents reinitiation at replicated origins.
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