Evidence map›Paper›PMID 19187758›Full record

ArticleMolecular cell2009

Maintenance of the DNA-damage checkpoint requires DNA-damage-induced mediator protein oligomerization.

Takehiko Usui, Steven S Foster, John H J Petrini

Abstract read
In one paragraph

Article in Molecular cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
–field-weighted citation impact
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

42 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. DNA damage checkpoint execution and the rules of its disengagement.Frontiers in cell and developmental biology · 2022
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Checkpoint Responses to DNA Double-Strand Breaks.Annual review of biochemistry · 2020
    Review
  12. Article
  13. Review
  14. Mec1Cell reports · 2019
    Article
  15. Activation of Tel1The Journal of biological chemistry · 2019
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Takehiko UsuiLaboratory of Chromosome Biology, Sloan-Kettering Institute, New York, NY 10065, USA.
Steven S Foster
John H J Petrini

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
ROLES OF MRELL AND RAD50 IN THE DNA DAMAGE RESPONSER01GM056888 · NIGMS · UNIVERSITY OF WISCONSIN MADISON · PI PETRINI, JOHN HJ · 1998 to 2019
$8.6M
Regulation of the DNA damage response by the Mre11 complexR37GM059413 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI PETRINI, JOHN HJ · 2012 to 2020
$5.2M
The Mre11 complex: linking recombination to checkpointsR01GM059413 · NIGMS · UNIVERSITY OF WISCONSIN MADISON · PI PETRINI, JOHN HJ · 1999 to 2011
$5.2M
FASEB SRC on Genetic Recombination and Genome RearrangementsR13CA162528 · NCI · FEDERATION OF AMER SOC FOR EXPER BIOLOGY · PI PETRINI, JOHN HJ · 2011 to 2011
$5k
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA08748NCI NIH HHS R13 CA162528NIGMS NIH HHS GM56888NIGMS NIH HHS GM59413NIGMS NIH HHS R01 GM056888NIGMS NIH HHS R01 GM059413NIGMS NIH HHS R37 GM059413
6 · The paper itself

Abstract

Oligomeric assembly of Brca1 C-terminal (BRCT) domain-containing mediator proteins occurs at sites of DNA damage. However, the functional significance and regulation of such assemblies are not well understood. In this study, we defined the molecular mechanism of DNA-damage-induced oligomerization of the S. cerevisiae BRCT protein Rad9. Our data suggest that Rad9's tandem BRCT domain mediates Rad9 oligomerization via its interaction with its own Mec1/Tel1-phosphorylated SQ/TQ cluster domain (SCD). Rad53 activation is unaffected by mutations that impair Rad9 oligomerization, but checkpoint maintenance is lost, indicating that oligomerization is required to sustain checkpoint signaling. Once activated, Rad53 phosphorylates the Rad9 BRCT domain, which attenuates the BRCT-SCD interaction. Failure to phosphorylate the Rad9 BRCT results in cytologically visible Rad9 foci. This suggests a feedback loop wherein Rad53 activity and Rad9 oligomerization are regulated to tune the DNA-damage response.

Indexed as

Binding SitesCell Cycle ProteinsCheckpoint Kinase 2DNA DamageDNA, FungalGenes, cdcIntracellular Signaling Peptides and ProteinsMutationPhosphorylationProtein Serine-Threonine KinasesProtein Structure, TertiarySaccharomyces cerevisiae ProteinsSignal TransductionCell Cycle ProteinsCheckpoint Kinase 2DNA, FungalIntracellular Signaling Peptides and ProteinsMEC1 protein, S cerevisiaeProtein Serine-Threonine KinasesRAD53 protein, S cerevisiaerad9 proteinSaccharomyces cerevisiae ProteinsTEL1 protein, S cerevisiae

Identifiers

PMID19187758
PMCPMC2995296

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Registered trials

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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.