The level of origin firing inversely affects the rate of replication fork progression

Zhong, Y., Nellimoottil, T., Peace, J. M., Knott, S. R., Villwock, S. K., Yee, J. M., Jancuska, J. M., Rege, S., Tecklenburg, M., Sclafani, R. A., Tavare, S., Aparicio, O. M. (April 2013) The level of origin firing inversely affects the rate of replication fork progression. J Cell Biol, 201 (3). pp. 373-83. ISSN 0021-9525

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URL: http://www.ncbi.nlm.nih.gov/pubmed/23629964
DOI: 10.1083/jcb.201208060

Abstract

DNA damage slows DNA synthesis at replication forks; however, the mechanisms remain unclear. Cdc7 kinase is required for replication origin activation, is a target of the intra-S checkpoint, and is implicated in the response to replication fork stress. Remarkably, we found that replication forks proceed more rapidly in cells lacking Cdc7 function than in wild-type cells. We traced this effect to reduced origin firing, which results in fewer replication forks and a consequent decrease in Rad53 checkpoint signaling. Depletion of Orc1, which acts in origin firing differently than Cdc7, had similar effects as Cdc7 depletion, consistent with decreased origin firing being the source of these defects. In contrast, mec1-100 cells, which initiate excess origins and also are deficient in checkpoint activation, showed slower fork progression, suggesting the number of active forks influences their rate, perhaps as a result of competition for limiting factors.

Item Type: Paper
Uncontrolled Keywords: Cell Cycle Checkpoints Cell Cycle Proteins/metabolism Checkpoint Kinase 2 DNA Damage *DNA Replication DNA, Fungal/biosynthesis/genetics Origin Recognition Complex/metabolism Protein-Serine-Threonine Kinases/metabolism *Replication Origin Saccharomyces cerevisiae/enzymology/*genetics Saccharomyces cerevisiae Proteins/metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
CSHL Authors:
Communities: CSHL Post Doctoral Fellows
CSHL labs > Hannon lab
Depositing User: Matt Covey
Date: 29 April 2013
Date Deposited: 18 Mar 2015 14:56
Last Modified: 18 Mar 2015 14:56
PMCID: PMC3639389
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31276

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