Evidence map›Paper›PMID 26368543›Full record

ArticlePLoS genetics2015

Critical Function of γH2A in S-Phase.

Eva Mejia-Ramirez, Oliver Limbo, Petra Langerak, Paul Russell

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

11 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
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  6. Sae2 antagonizes Rad9 accumulation at DNA double-strand breaks to attenuate checkpoint signaling and facilitate end resection.Proceedings of the National Academy of Sciences of the United States of America · 2018
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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

4 authors at 1 institution in 1 country.

Eva Mejia-RamirezDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Oliver LimboDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Petra LangerakDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Paul RussellDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Scripps Research Institute · US

Funding

Yeast Genetics and Stress Response Genes-BiomedicalP42ES010337 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2000 to 2022
$69.8M
Studies of the DNA damage checkpointsR01CA077325 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI RUSSELL, PAUL · 1998 to 2017
$7.1M
Studies of the DNA Replication CheckpointR01GM059447 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI RUSSELL, PAUL · 1999 to 2016
$6.0M
Mre11/Rad50 Structural Biology for DNA Damage ResponsesR01CA117638 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI RUSSELL, PAUL, TAINER, JOHN A. · 2005 to 2019
$5.6M
NCI NIH HHS CA077325NCI NIH HHS CA117638NCI NIH HHS R01 CA077325NCI NIH HHS R01 CA117638NIEHS NIH HHS P42 ES010337NIEHS NIH HHS P42ES010337NIGMS NIH HHS GM059447NIGMS NIH HHS R01 GM059447
6 · The paper itself

Abstract

Phosphorylation of histone H2AX by ATM and ATR establishes a chromatin recruitment platform for DNA damage response proteins. Phospho-H2AX (γH2AX) has been most intensively studied in the context of DNA double-strand breaks caused by exogenous clastogens, but recent studies suggest that DNA replication stress also triggers formation of γH2A (ortholog of γH2AX) in Schizosaccharomyces pombe. Here, a focused genetic screen in fission yeast reveals that γH2A is critical when there are defects in Replication Factor C (RFC), which loads proliferating cell nuclear antigen (PCNA) clamp onto duplex DNA. Surprisingly Chk1, Cds1/Chk2 and the Rad9-Hus1-Rad1 checkpoint clamp, which are crucial for surviving many genotoxins, are fully dispensable in RFC-defective cells. Immunoblot analysis confirms that Rad9-Hus1-Rad1 is not required for formation of γH2A by Rad3/ATR in S-phase. Defects in DNA polymerase epsilon, which binds PCNA in the replisome, also create an acute need for γH2A. These requirements for γH2A were traced to its role in docking with Brc1, which is a 6-BRCT-domain protein that is structurally related to budding yeast Rtt107 and mammalian PTIP. Brc1, which localizes at stalled replication forks by binding γH2A, prevents aberrant formation of Replication Protein A (RPA) foci in RFC-impaired cells, suggesting that Brc1-coated chromatin stabilizes replisomes when PCNA or DNA polymerase availability limits DNA synthesis.

Indexed as

S PhaseDNA, FungalDNA Polymerase IIHistonesMutationProliferating Cell Nuclear AntigenProtein BindingSchizosaccharomycesSchizosaccharomyces pombe ProteinsDNA, FungalDNA Polymerase IIHistonesProliferating Cell Nuclear AntigenSchizosaccharomyces pombe Proteins

Identifiers

PMID26368543
PMCPMC4569340
OpenAlexW2235488734

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.