Evidence map›Paper›PMID 21777809›Full record

ArticleMolecular cell2011

ATR autophosphorylation as a molecular switch for checkpoint activation.

Shizhou Liu, Bunsyo Shiotani, Mayurika Lahiri, Alexandre Maréchal, Alice Tse, Charles Chung Yun Leung, J N Mark Glover, Xiaohong H Yang, Lee Zou

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers.

0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed
8.7field-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

168 citing papers in PubMed, 262 citations in OpenAlex.

  1. Review
  2. Article
  3. Capturing ATR-ATRIP in the act of activation.Nature structural & molecular biology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. DNA Damage and Replication Stress Checkpoints.Annual review of biochemistry · 2025
    Review
  17. Article
  18. Article
  19. Review
  20. Article

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

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

9 authors at 2 institutions in 3 countries.

Shizhou LiuMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
Bunsyo Shiotani
Mayurika Lahiri
Alexandre Maréchal
Alice Tse
Charles Chung Yun Leung
J N Mark Glover
Xiaohong H Yang
Lee Zou
Harvard University · USUniversity of Alberta · CA

Funding

Regulation of the ATR Checkpoint Kinase by DNA DamageR01GM076388 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI ZOU, LEE · 2006 to 2018
$4.3M
NIGMS NIH HHS GM076388NIGMS NIH HHS R01 GM076388
6 · The paper itself

Abstract

The ataxia telangiectasia-mutated and Rad3-related (ATR) kinase is a master checkpoint regulator safeguarding the genome. Upon DNA damage, the ATR-ATRIP complex is recruited to sites of DNA damage by RPA-coated single-stranded DNA and activated by an elusive process. Here, we show that ATR is transformed into a hyperphosphorylated state after DNA damage, and that a single autophosphorylation event at Thr 1989 is crucial for ATR activation. Phosphorylation of Thr 1989 relies on RPA, ATRIP, and ATR kinase activity, but unexpectedly not on the ATR stimulator TopBP1. Recruitment of ATR-ATRIP to RPA-ssDNA leads to congregation of ATR-ATRIP complexes and promotes Thr 1989 phosphorylation in trans. Phosphorylated Thr 1989 is directly recognized by TopBP1 via the BRCT domains 7 and 8, enabling TopBP1 to engage ATR-ATRIP, to stimulate the ATR kinase, and to facilitate ATR substrate recognition. Thus, ATR autophosphorylation on RPA-ssDNA is a molecular switch to launch robust checkpoint response.

Indexed as

Adaptor Proteins, Signal TransducingAtaxia Telangiectasia Mutated ProteinsCarrier ProteinsCell Cycle ProteinsCells, CulturedDNA-Binding ProteinsDNA DamageDNA, Single-StrandedGenes, cdcGenes, SwitchHumansNuclear ProteinsPhosphorylationProtein Serine-Threonine KinasesReplication Protein AThreonineAdaptor Proteins, Signal TransducingAtaxia Telangiectasia Mutated ProteinsATRIP protein, humanATR protein, humanCarrier ProteinsCell Cycle ProteinsDNA-Binding ProteinsDNA, Single-StrandedNuclear ProteinsProtein Serine-Threonine KinasesReplication Protein ARPA1 protein, humanThreonineTOPBP1 protein, human

Identifiers

PMID21777809
PMCPMC3155885
OpenAlexW2009779043

What OpenQuestion holds

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LicenceTDM
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.