The Journal of Cell Biology
Geisel School of Medicine
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.
Caldwell JM, Chen Y, Schollaert KL, Theis JF, Babcock GF, Newlon CS, Sanchez Y. Orchestration of the S-phase and DNA damage checkpoint pathways by replication forks from early origins. J Cell Biol. 2008 Mar 24;180(6):1073-86. doi: 10.1083/jcb.200706009. Epub 2008 Mar 17. PMID: 18347065; PMCID: PMC2290838.
Dartmouth Digital Commons Citation
Caldwell, Julie M.; Chen, Yinhuai; Schollaert, Kaila L.; Theis, James F.; Babcock, George F.; Newlon, Carol S.; and Sanchez, Yolanda, "Orchestration of the S-phase and DNA Damage Checkpoint Pathways by Replication Forks from Early Origins" (2008). Dartmouth Scholarship. 3024.