Evidence map›Paper›PMID 25449133›Full record

ArticleMolecular cell2014

Strand-specific analysis shows protein binding at replication forks and PCNA unloading from lagging strands when forks stall.

Chuanhe Yu, Haiyun Gan, Junhong Han, Zhi-Xiong Zhou, Shaodong Jia, Andrei Chabes, Gianrico Farrugia, Tamas Ordog, Zhiguo Zhang

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 137 papers.

0numbers the graph read from it
0cells of the map it votes in
137citing papers in PubMed
10.0field-weighted citation impact, top 1% 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

137 citing papers in PubMed, 196 citations in OpenAlex.

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  16. Interstitial telomeric sequences promote gross chromosomal rearrangement via multiple mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  17. Clamping Pol ε to the leading strand.Nature structural & molecular biology · 2024
    Article
  18. Article
  19. Article
  20. Article

77 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Chuanhe YuDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Haiyun GanDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Junhong HanDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Zhi-Xiong ZhouDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Shaodong JiaDepartment of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
Andrei ChabesDepartment of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
Gianrico FarrugiaDivision of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Center for Individualized Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Tamas OrdogCenter for Individualized Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Zhiguo ZhangDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Center for Individualized Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. Electronic address: zhang.zhiguo@mayo.edu.
Mayo Clinic · USUmeå University · SE

Funding

Physiological Characterization and Data Integration CoreP01DK068055 · NIDDK · MAYO CLINIC ROCHESTER · PI ORDOG, TAMAS · 2004 to 2019
$23.8M
PILOT AND FEASIBILTY PROGRAMP30DK084567 · NIDDK · MAYO CLINIC ROCHESTER · PI GREGORY J. GORES · 2009 to 2026
$22.2M
Interstitial Cells of Cajal in Diabetic GastropathyR01DK058185 · NIDDK · UNIVERSITY OF NEVADA RENO · PI ORDOG, TAMAS · 2002 to 2020
$5.2M
Histone chaperones and transcriptional silencingR01GM072719 · NIGMS · MAYO CLINIC ROCHESTER · PI ZHANG, ZHIGUO · 2005 to 2015
$2.9M
Regulation of Nucleosome AssemblyR01GM081838 · NIGMS · MAYO CLINIC ROCHESTER · PI ZHANG, ZHIGUO · 2008 to 2015
$2.4M
The role of a histone H4 phosphorylation in drug resistanceR01CA157489 · NCI · MAYO CLINIC ROCHESTER · PI ZHANG, ZHIGUO · 2012 to 2016
$1.6M
NCI NIH HHS R01 CA157489NIDDK NIH HHS P01 DK068055NIDDK NIH HHS P30 DK084567NIDDK NIH HHS R01 DK058185NIGMS NIH HHS GM72719NIGMS NIH HHS GM81838NIGMS NIH HHS R01 GM072719NIGMS NIH HHS R01 GM081838
6 · The paper itself

Abstract

In eukaryotic cells, DNA replication proceeds with continuous synthesis of leading-strand DNA and discontinuous synthesis of lagging-strand DNA. Here we describe a method, eSPAN (enrichment and sequencing of protein-associated nascent DNA), which reveals the genome-wide association of proteins with leading and lagging strands of DNA replication forks. Using this approach in budding yeast, we confirm the strand specificities of DNA polymerases delta and epsilon and show that the PCNA clamp is enriched at lagging strands compared with leading-strand replication. Surprisingly, at stalled forks, PCNA is unloaded specifically from lagging strands. PCNA unloading depends on the Elg1-containing alternative RFC complex, ubiquitination of PCNA, and the checkpoint kinases Mec1 and Rad53. Cells deficient in PCNA unloading exhibit increased chromosome breaks. Our studies provide a tool for studying replication-related processes and reveal a mechanism whereby checkpoint kinases regulate strand-specific unloading of PCNA from stalled replication forks to maintain genome stability.

Indexed as

DNA ReplicationChromatin ImmunoprecipitationChromosomes, FungalDNA DamageDNA, FungalDNA Polymerase IIDNA Polymerase IIIGenomic InstabilityProliferating Cell Nuclear AntigenProtein BindingSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Analysis, DNAUbiquitinationDNA, FungalDNA Polymerase IIDNA Polymerase IIIProliferating Cell Nuclear AntigenSaccharomyces cerevisiae Proteins

Identifiers

PMID25449133
PMCPMC4362665
OpenAlexW2137278429

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.