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Published January 2017 | Supplemental Material
Journal Article Open

Mutations in the Non-Catalytic Subunit Dpb2 of DNA Polymerase Epsilon Affect the Nrm1 Branch of the DNA Replication Checkpoint


To preserve genome integrity, the S-phase checkpoint senses damaged DNA or nucleotide depletion and when necessary, arrests replication progression and delays cell division. Previous studies, based on two pol2 mutants have suggested the involvement of DNA polymerase epsilon (Pol ε) in sensing DNA replication accuracy in Saccharomyces cerevisiae. Here we have studied the involvement of Pol ε in sensing proper progression of DNA replication, using a mutant in DPB2, the gene coding for a non-catalytic subunit of Pol ε. Under genotoxic conditions, the dpb2-103 cells progress through S phase faster than wild-type cells. Moreover, the Nrm1-dependent branch of the checkpoint, which regulates the expression of many replication checkpoint genes, is impaired in dpb2-103 cells. Finally, deletion of DDC1 in the dpb2-103 mutant is lethal supporting a model of strand-specific activation of the replication checkpoint. This lethality is suppressed by NRM1 deletion. We postulate that improper activation of the Nrm1-branch may explain inefficient replication checkpoint activation in Pol ε mutants.

Additional Information

© 2017 Dmowski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: May 16, 2016; Accepted: January 5, 2017; Published: January 20, 2017. We thank Dr. Karolina Makiela-Dzbenska for assistance with strain construction. Author Contributions: Conceptualization: MD JLC PJ IJF. Formal analysis: MD JR PJ IJF. Funding acquisition: PJ IJF. Investigation: MD JR. Visualization: MD. Writing - original draft: MD. Writing - review & editing: MD JLC PJ IJF. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. This study was supported by grant no. 5714/B/P01/2010/39 from the Ministry of Science and Higher Education, Poland (www.ncn.gov.pl) to PJ and grant no. TEAM/2011-8/1 from the Foundation for Polish Science (www.fnp.org.pl), co-financed from European Union - Regional Development Fund "New players involved in the maintenance of genomic stability" to IJF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have declared that no competing interests exist.

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