Evidence map›Paper›PMID 15226425›Full record

ArticleMolecular and cellular biology2004

Histone H2A phosphorylation controls Crb2 recruitment at DNA breaks, maintains checkpoint arrest, and influences DNA repair in fission yeast.

Toru M Nakamura, Li-Lin Du, Christophe Redon, Paul Russell

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2004. 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 103 papers.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed
7.6field-weighted citation impact, top 2% 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

103 citing papers in PubMed, 195 citations in OpenAlex.

  1. Article
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  14. Nucleosome Remodeling by Fun30Frontiers in molecular biosciences · 2019
    Review
  15. 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
    Article
  16. Mre11 complex links sister chromatids to promote repair of a collapsed replication fork.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Toru M NakamuraDepartment of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. nakamut@scripps.edu
Li-Lin Du
Christophe Redon
Paul Russell
National Institutes of Health · USScripps Research Institute · US

Funding

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
NCI NIH HHS CA77325NCI NIH HHS R01 CA077325NIGMS NIH HHS GM59447NIGMS NIH HHS R01 GM059447
6 · The paper itself

Abstract

Mammalian ATR and ATM checkpoint kinases modulate chromatin structures near DNA breaks by phosphorylating a serine residue in the carboxy-terminal tail SQE motif of histone H2AX. Histone H2A is similarly regulated in Saccharomyces cerevisiae. The phosphorylated forms of H2AX and H2A, known as gamma-H2AX and gamma-H2A, are thought to be important for DNA repair, although their evolutionarily conserved roles are unknown. Here, we investigate gamma-H2A in the fission yeast Schizosaccharomyces pombe. We show that formation of gamma-H2A redundantly requires the ATR/ATM-related kinases Rad3 and Tel1. Mutation of the SQE motif to AQE (H2A-AQE) in the two histone H2A genes caused sensitivity to a wide range of genotoxic agents, increased spontaneous DNA damage, and impaired checkpoint maintenance. The H2A-AQE mutations displayed a striking synergistic interaction with rad22Delta (Rad52 homolog) in ionizing radiation (IR) survival. These phenotypes correlated with defective phosphorylation of the checkpoint proteins Crb2 and Chk1 and a failure to recruit large amounts of Crb2 to damaged DNA. Surprisingly, the H2A-AQE mutations substantially suppressed the IR hypersensitivity of crb2Delta cells by a mechanism that required the RecQ-like DNA helicase Rqh1. We propose that gamma-H2A modulates checkpoint and DNA repair through large-scale recruitment of Crb2 to damaged DNA. This function correlates with evidence that gamma-H2AX regulates recruitment of several BRCA1 carboxyl terminus domain-containing proteins (NBS1, 53BP1, MDC1/NFBD1, and BRCA1) in mammals.

Indexed as

DNA DamageDNA RepairAmino Acid SequenceAnimalsCell CycleCell Cycle ProteinsCheckpoint Kinase 2DNA HelicasesEpistasis, GeneticFungal ProteinsGenomic InstabilityHistonesHumansIntracellular Signaling Peptides and ProteinsMolecular Sequence DataMutationCell Cycle ProteinsCheckpoint Kinase 2Crb2 protein, S pombeDNA HelicasesFungal ProteinsHistonesIntracellular Signaling Peptides and ProteinsNuclear ProteinsProtein KinasesProtein Serine-Threonine Kinasesrad3 protein, S pombeRqh1 protein, S pombeSaccharomyces cerevisiae ProteinsSchizosaccharomyces pombe ProteinsTEL1 protein, S cerevisiaetel1 protein, S pombe

Identifiers

PMID15226425
PMCPMC434244
OpenAlexW2121554894

What OpenQuestion holds

Textmetadata
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.