Evidence map›Paper›PMID 15964794›Full record

ArticleMolecular and cellular biology2005

ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1.

Zhongsheng You, Charly Chahwan, Julie Bailis, Tony Hunter, Paul Russell

Abstract read
In one paragraph

Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 246 papers.

0numbers the graph read from it
0cells of the map it votes in
246citing papers in PubMed
14.0field-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

246 citing papers in PubMed, 421 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. DNA Damage and Replication Stress Checkpoints.Annual review of biochemistry · 2025
    Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Dynamic Properties of the DNA Damage Response Mre11/Rad50 Complex.International journal of molecular sciences · 2023
    Review
  18. Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism.International journal of molecular sciences · 2023
    Review
  19. Article
  20. Review

186 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

5 authors at 2 institutions in 1 country.

Zhongsheng YouMolecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Charly Chahwan
Julie Bailis
Tony Hunter
Paul Russell
Salk Institute for Biological Studies · USScripps Research Institute · US

Funding

SOMATIC CELL CYCLE REGULATION BY PHOSPHORYLATIONR01CA080100 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI HUNTER, TONY R. · 1999 to 2018
$13.1M
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 CA80100NCI NIH HHS R01 CA077325NCI NIH HHS R01 CA080100NIGMS NIH HHS GM59447NIGMS NIH HHS R01 GM059447
6 · The paper itself

Abstract

ATM has a central role in controlling the cellular responses to DNA damage. It and other phosphoinositide 3-kinase-related kinases (PIKKs) have giant helical HEAT repeat domains in their amino-terminal regions. The functions of these domains in PIKKs are not well understood. ATM activation in response to DNA damage appears to be regulated by the Mre11-Rad50-Nbs1 (MRN) complex, although the exact functional relationship between the MRN complex and ATM is uncertain. Here we show that two pairs of HEAT repeats in fission yeast ATM (Tel1) interact with an FXF/Y motif at the C terminus of Nbs1. This interaction resembles nucleoporin FXFG motif binding to HEAT repeats in importin-beta. Budding yeast Nbs1 (Xrs2) appears to have two FXF/Y motifs that interact with Tel1 (ATM). In Xenopus egg extracts, the C terminus of Nbs1 recruits ATM to damaged DNA, where it is subsequently autophosphorylated. This interaction is essential for ATM activation. A C-terminal 147-amino-acid fragment of Nbs1 that has the Mre11- and ATM-binding domains can restore ATM activation in an Nbs1-depleted extract. We conclude that an interaction between specific HEAT repeats in ATM and the C-terminal FXF/Y domain of Nbs1 is essential for ATM activation. We propose that conformational changes in the MRN complex that occur upon binding to damaged DNA are transmitted through the FXF/Y-HEAT interface to activate ATM. This interaction also retains active ATM at sites of DNA damage.

Indexed as

Amino Acid MotifsAmino Acid SequenceAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell ExtractsChromosomal Proteins, Non-HistoneConserved SequenceDNA-Binding ProteinsDNA DamageFemaleFungal ProteinsHumansModels, BiologicalModels, MolecularMolecular Sequence DataAtaxia Telangiectasia Mutated ProteinsATM protein, humanCell Cycle ProteinsCell ExtractsChromosomal Proteins, Non-HistoneDNA-Binding ProteinsFungal ProteinsNBN protein, XenopusNbs1 protein, S pombeProtein Serine-Threonine KinasesSchizosaccharomyces pombe ProteinsTumor Suppressor ProteinsXenopus Proteins

Identifiers

PMID15964794
PMCPMC1156989
OpenAlexW2100285961

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.