Orchestration of the S-phase and DNA damage checkpoint pathways by replication forks from early origins
Autor: | George F. Babcock, James F. Theis, Carol S. Newlon, Yinhuai Chen, Yolanda Sanchez, Kaila L. Schollaert, Julie M. Caldwell |
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Rok vydání: | 2008 |
Předmět: |
DNA Replication
DNA re-replication Genome instability Saccharomyces cerevisiae Proteins Time Factors Cell cycle checkpoint DNA damage Cell Cycle Proteins Saccharomyces cerevisiae Protein Serine-Threonine Kinases Biology Genomic Instability Article S Phase 03 medical and health sciences Control of chromosome duplication Cyclins Gene Expression Regulation Fungal Research Articles 030304 developmental biology Genetics 0303 health sciences 030302 biochemistry & molecular biology DNA replication Cell Biology G2-M DNA damage checkpoint DNA Replication Fork Cyclin-Dependent Kinases Cell biology Genes cdc Cell Transformation Neoplastic Checkpoint Kinase 1 Protein Kinases Cell Division DNA Damage |
Zdroj: | The Journal of Cell Biology |
ISSN: | 1540-8140 0021-9525 |
Popis: | The S-phase checkpoint activated at replication forks coordinates DNA replication when forks stall because of DNA damage or low deoxyribonucleotide triphosphate pools. We explore the involvement of replication forks in coordinating the S-phase checkpoint using dun1Δ cells that have a defect in the number of stalled forks formed from early origins and are dependent on the DNA damage Chk1p pathway for survival when replication is stalled. We show that providing additional origins activated in early S phase and establishing a paused fork at a replication fork pause site restores S-phase checkpoint signaling to chk1Δ dun1Δ cells and relieves the reliance on the DNA damage checkpoint pathway. Origin licensing and activation are controlled by the cyclin–Cdk complexes. Thus, oncogene-mediated deregulation of cyclins in the early stages of cancer development could contribute to genomic instability through a deficiency in the forks required to establish the S-phase checkpoint. |
Databáze: | OpenAIRE |
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