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A variable fork rate affects timing of origin firing and S phase dynamics in Saccharomyces cerevisiae

Paper ID Volume ID Publish Year Pages File Format Full-Text
23367 43439 2013 11 PDF Available
Title
A variable fork rate affects timing of origin firing and S phase dynamics in Saccharomyces cerevisiae
Abstract

•Replication origins are activated at definite timing but with different efficiency.•Fork rate changes affect efficiency of origin activation for a timely S phase.•Modulation of the fork rate controls the timing of origin activation during S phase.•Fork rate, firing time and origin density affect efficient origin firing.•Prediction of firing efficiency for various origins can be testable experimentally.

Activation (in the following referred to as firing) of replication origins is a continuous and irreversible process regulated by availability of DNA replication molecules and cyclin-dependent kinase activities, which are often altered in human cancers. The temporal, progressive origin firing throughout S phase appears as a characteristic replication profile, and computational models have been developed to describe this process. Although evidence from yeast to human indicates that a range of replication fork rates is observed experimentally in order to complete a timely S phase, those models incorporate velocities that are uniform across the genome. Taking advantage of the availability of replication profiles, chromosomal position and replication timing, here we investigated how fork rate may affect origin firing in budding yeast. Our analysis suggested that patterns of origin firing can be observed from a modulation of the fork rate that strongly correlates with origin density. Replication profiles of chromosomes with a low origin density were fitted with a variable fork rate, whereas for the ones with a high origin density a constant fork rate was appropriate. This indeed supports the previously reported correlation between inter-origin distance and fork rate changes. Intriguingly, the calculated correlation between fork rate and timing of origin firing allowed the estimation of firing efficiencies for the replication origins. This approach correctly retrieved origin efficiencies previously determined for chromosome VI and provided testable prediction for other chromosomal origins. Our results gain deeper insights into the temporal coordination of genome duplication, indicating that control of the replication fork rate is required for the timely origin firing during S phase.

Keywords
DNA replication; Origin firing; Replication timing; Replication fork rate; Firing efficiency; Budding yeast
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A variable fork rate affects timing of origin firing and S phase dynamics in Saccharomyces cerevisiae
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 168, Issue 2, 20 October 2013, Pages 174–184
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us