Evidence map›Paper›PMID 30598452›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

Mcm10 has potent strand-annealing activity and limits translocase-mediated fork regression.

Ryan Mayle, Lance Langston, Kelly R Molloy, Dan Zhang, Brian T Chait, Michael E O'Donnell

Open access · bronzeAbstract readVideo-Audio Media
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.2field-weighted citation impact, top 11% 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

34 citing papers in PubMed, 48 citations in OpenAlex.

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  12. Mechanism of eukaryotic origin unwinding is a dual helicase DNA shearing process.Proceedings of the National Academy of Sciences of the United States of America · 2023
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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 2 institutions in 1 country.

Ryan MayleLaboratory of DNA Replication, The Rockefeller University, New York, NY 10065.
Lance LangstonLaboratory of DNA Replication, The Rockefeller University, New York, NY 10065.ORCID 0000-0002-2736-9284
Kelly R MolloyLaboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10065.
Dan ZhangLaboratory of DNA Replication, The Rockefeller University, New York, NY 10065.
Brian T ChaitLaboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10065 Brian.Chait@rockefeller.edu odonnel@rockefeller.edu.
Michael E O'DonnellLaboratory of DNA Replication, The Rockefeller University, New York, NY 10065; Brian.Chait@rockefeller.edu odonnel@rockefeller.edu.
Rockefeller University · USHoward Hughes Medical Institute · US

Funding

TR&D Project 4. The Imaging Stage: Multiscale Spatiotemporal Modeling of Macromolecular Systems in Cellular NeighborhoodsP41GM109824 · NIGMS · ROCKEFELLER UNIVERSITY · PI ROUT, MICHAEL P · 2014 to 2023
$18.8M
National Resource for Mass Spectrom of Biological MacromoleculesP41GM103314 · NIGMS · ROCKEFELLER UNIVERSITY · PI CHAIT, BRIAN T · 2012 to 2017
$9.9M
Mechanisms of Cell Regulation and TransformationT32CA009673 · NCI · ROCKEFELLER UNIVERSITY · PI KAPOOR, TARUN M. · 1991 to 2018
$7.0M
Biochemical Mechanism and Structure of the Eukaryotic Replication ForkR01GM115809 · NIGMS · ROCKEFELLER UNIVERSITY · PI O'DONNELL, MICHAEL E · 2015 to 2022
$2.6M
Howard Hughes Medical InstituteNCI NIH HHS T32 CA009673NIGMS NIH HHS P41 GM103314NIGMS NIH HHS P41 GM109824NIGMS NIH HHS R01 GM115809
6 · The paper itself

Abstract

The 11-subunit eukaryotic replicative helicase CMG (Cdc45, Mcm2-7, GINS) tightly binds Mcm10, an essential replication protein in all eukaryotes. Here we show that Mcm10 has a potent strand-annealing activity both alone and in complex with CMG. CMG-Mcm10 unwinds and then reanneals single strands soon after they have been unwound in vitro. Given the DNA damage and replisome instability associated with loss of Mcm10 function, we examined the effect of Mcm10 on fork regression. Fork regression requires the unwinding and pairing of newly synthesized strands, performed by a specialized class of ATP-dependent DNA translocases. We show here that Mcm10 inhibits fork regression by the well-known fork reversal enzyme SMARCAL1. We propose that Mcm10 inhibits the unwinding of nascent strands to prevent fork regression at normal unperturbed replication forks, either by binding the fork junction to form a block to SMARCAL1 or by reannealing unwound nascent strands to their parental template. Analysis of the CMG-Mcm10 complex by cross-linking mass spectrometry reveals Mcm10 interacts with six CMG subunits, with the DNA-binding region of Mcm10 on the N-face of CMG. This position on CMG places Mcm10 at the fork junction, consistent with a role in regulating fork regression.

Indexed as

DNA ReplicationDNADNA HelicasesHumansMass SpectrometryMinichromosome Maintenance ProteinsReplication Protein ASaccharomyces cerevisiae ProteinsDNADNA HelicasesMCM10 protein, S cerevisiaeMinichromosome Maintenance ProteinsReplication Protein ASaccharomyces cerevisiae ProteinsSMARCAL1 protein, humanCMG helicaseDNA replicationfork regressionMcm10SMARCAL1

Identifiers

PMID30598452
PMCPMC6338834
OpenAlexW2906985795

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.