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 re...

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Bibliographic Details
Published in:PLoS genetics 2017-01, Vol.13 (1), p.e1006572-e1006572
Main Authors: Dmowski, Michał, Rudzka, Justyna, Campbell, Judith L, Jonczyk, Piotr, Fijałkowska, Iwona J
Format: Article
Language:English
Subjects:
Biology and life sciences
Biophysics
Cell cycle
Cell division
Deoxyribonucleic acid
DNA
DNA damage
DNA Polymerase II - genetics
DNA Polymerase II - metabolism
DNA replication
Evacuations & rescues
Funding
Gene mutation
Genomes
Kinases
Mutation
Phosphorylation
Proteins
Repressor Proteins - genetics
Repressor Proteins - metabolism
Research and Analysis Methods
S Phase - genetics
Saccharomyces cerevisiae
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Yeast
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Summary: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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1006572