Evidence map›Paper›PMID 25870112›Full record

ArticleMolecular and cellular biology2015

Mcm2-7 Is an Active Player in the DNA Replication Checkpoint Signaling Cascade via Proposed Modulation of Its DNA Gate.

Feng-Ling Tsai, Sriram Vijayraghavan, Joseph Prinz, Heather K MacAlpine, David M MacAlpine, Anthony Schwacha

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 16 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Feng-Ling TsaiDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Sriram VijayraghavanDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Joseph PrinzDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
Heather K MacAlpineDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
David M MacAlpineDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
Anthony SchwachaDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA schwacha@pitt.edu.
University of Pittsburgh · USDuke University Hospital · USDuke Medical Center · US

Funding

The Role of the MCM2-7 Complex in the Replication Fork ProcessivityR01GM083985 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SCHWACHA, ANTHONY · 2009 to 2013
$1.3M
Chromatin architecture defines DNA replication originsR01GM104097 · NIGMS · DUKE UNIVERSITY · PI MACALPINE, DAVID M · 2013 to 2016
$1.2M
NIGMS NIH HHS R01 GM083985NIGMS NIH HHS R01GM083985NIGMS NIH HHS R01 GM104097NIGMS NIH HHS R01GM104097
6 · The paper itself

Abstract

The DNA replication checkpoint (DRC) monitors and responds to stalled replication forks to prevent genomic instability. How core replication factors integrate into this phosphorylation cascade is incompletely understood. Here, through analysis of a unique mcm allele targeting a specific ATPase active site (mcm2DENQ), we show that the Mcm2-7 replicative helicase has a novel DRC function as part of the signal transduction cascade. This allele exhibits normal downstream mediator (Mrc1) phosphorylation, implying DRC sensor kinase activation. However, the mutant also exhibits defective effector kinase (Rad53) activation and classic DRC phenotypes. Our previous in vitro analysis showed that the mcm2DENQ mutation prevents a specific conformational change in the Mcm2-7 hexamer. We infer that this conformational change is required for its DRC role and propose that it allosterically facilitates Rad53 activation to ensure a replication-specific checkpoint response.

Indexed as

DNA ReplicationCatalytic DomainCell Cycle ProteinsCheckpoint Kinase 2DNA-Binding ProteinsDNA, FungalMinichromosome Maintenance ProteinsMutationNuclear ProteinsProtein MultimerizationSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSignal TransductionCDC45 protein, S cerevisiaeCell Cycle ProteinsCheckpoint Kinase 2DNA-Binding ProteinsDNA, FungalMCM2 protein, S cerevisiaeMinichromosome Maintenance ProteinsNuclear ProteinsRAD53 protein, S cerevisiaeSaccharomyces cerevisiae Proteins

Identifiers

PMID25870112
PMCPMC4438241
OpenAlexW2080832391

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.