Checkpoint-independent scaling of the Saccharomyces cerevisiaeDNA replication program

BMC Biology

Research Article

Naama Barkai¹  Miri Carmi¹  Ariel Gispan¹ 

[1] Department of Molecular Genetics, Weizmann Institute of Science, 76100, Rehovot, Israel;

关键词: mrc1;    Checkpoint;    Replication timing;   

DOI  :  10.1186/s12915-014-0079-z

 received in 2014-09-17, accepted in 2014-09-18,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundIn budding yeast, perturbations that prolong S phase lead to a proportionate delay in the activation times of most origins. The DNA replication checkpoint was implicated in this scaling phenotype, as an intact checkpoint was shown to be required for the delayed activation of late origins in response to hydroxyurea treatment. In support of that, scaling is lost in cells deleted of mrc1, a mediator of the replication checkpoint signal. Mrc1p, however, also plays a role in normal replication.ResultsTo examine whether the replication checkpoint is required for scaling the replication profile with S phase duration we measured the genome-wide replication profile of different MRC1 alleles that separate its checkpoint function from its role in normal replication, and further analyzed the replication profiles of S phase mutants that are checkpoint deficient. We found that the checkpoint is not required for scaling; rather the unique replication phenotype of mrc1 deleted cells is attributed to the role of Mrc1 in normal replication. This is further supported by the replication profiles of tof1Δ which functions together with Mrc1p in normal replication, and by the distinct replication profiles of specific POL2 alleles which differ in their interaction with Mrc1p.ConclusionsWe suggest that the slow fork progression in mrc1 deleted cells reduces the likelihood of passive replication leading to the activation of origins that remain mostly dormant in wild-type cells.

【 授权许可】

Unknown   
© Gispan et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.