2017
DOI: 10.1371/journal.pgen.1006572
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Mutations in the Non-Catalytic Subunit Dpb2 of DNA Polymerase Epsilon Affect the Nrm1 Branch of the DNA Replication Checkpoint

Abstract: 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 … Show more

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Cited by 9 publications
(11 citation statements)
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“…Some Dpb2 mutants exhibited a mutator phenotype comparable to that of mismatch-repair-defective strains (msh6), indicating that defects in the B-subunit of the human Pol⑀ gene can induce genomic instability. The structure of p59 -p261 C provides a rationale for explanation of the effects of amino acid changes in the yeast Pol⑀ B-subunit, characterized by weakened interaction with the catalytic subunit and the GINS complex, elevated spontaneous mutagenesis, and the affected Nrm1 branch of the DNA replication checkpoint (11,21,28,29,40,48).…”
Section: Crystal Structure Of Human Pol⑀ P59 -P261 C Complex the P59 mentioning
confidence: 99%
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“…Some Dpb2 mutants exhibited a mutator phenotype comparable to that of mismatch-repair-defective strains (msh6), indicating that defects in the B-subunit of the human Pol⑀ gene can induce genomic instability. The structure of p59 -p261 C provides a rationale for explanation of the effects of amino acid changes in the yeast Pol⑀ B-subunit, characterized by weakened interaction with the catalytic subunit and the GINS complex, elevated spontaneous mutagenesis, and the affected Nrm1 branch of the DNA replication checkpoint (11,21,28,29,40,48).…”
Section: Crystal Structure Of Human Pol⑀ P59 -P261 C Complex the P59 mentioning
confidence: 99%
“…Historically, subunits in different organisms were named differently, and the current nomenclature of polymerase subunits is shown in Table 1. The B-subunits stabilize the catalytic subunit (11,12), act as scaffolding proteins to mediate interactions with other components of the replication machinery (13)(14)(15)(16), and regulate DNA-synthesizing activity in a cell cycle-dependent manner, during checkpoints, and telomere maintenance (17)(18)(19)(20)(21).…”
mentioning
confidence: 99%
“…In dpb2 - 103 cells transcriptional activation of MBF-dependent G1/S transition was faster and, more importantly, prematurely switched off, when compared to the wild type cells (Fig. 1 ) (Dmowski et al 2017 ). Thus these observations may be the starting point for investigations of the effect of mutations in the Dpb2 subunit on the transcription of G1/S transition genes and its consequences for the cell cycle progression and genome stability.…”
Section: Polymerase ε and The S Phase Checkpointmentioning
confidence: 97%
“…However, the mechanism has not been identified because C-terminal mutations in the catalytic subunit Pol2 give very sick cells and their characterization is difficult. Recently, the involvement of the essential non-catalytic subunit Dpb2 in the response to the replication stress has been demonstrated by studies of the dpb2 - 103 mutant (Dmowski et al 2017 ). Yeast cells, when challenged with the RNR inhibitor hydroxyurea, activate the Rad53 checkpoint kinase, which in turn activate the Dun1–Crt1 branch (mainly dNTP upregulation) and the MBF-Nrm1 branch, which stimulates the transcription of G1/S transition genes (explained below) (Bastos de Oliveira et al 2012 ; Hustedt et al 2013 ).…”
Section: Polymerase ε and The S Phase Checkpointmentioning
confidence: 99%
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