Evidence map›Paper›PMID 18936170›Full record

ArticleMolecular and cellular biology2008

The basic cleft of RPA70N binds multiple checkpoint proteins, including RAD9, to regulate ATR signaling.

Xin Xu, Sivaraja Vaithiyalingam, Gloria G Glick, Daniel A Mordes, Walter J Chazin, David Cortez

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed
6.6field-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

111 citing papers in PubMed, 171 citations in OpenAlex.

  1. Article
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  12. Fission yeast Ase1Molecular biology research communications · 2021
    Article
  13. Article
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  15. Novel insights into the mechanism of cell cycle kinases Mec1(ATR) and Tel1(ATM).Critical reviews in biochemistry and molecular biology · 2021
    Article
  16. Review
  17. Article
  18. RPA-mediated recruitment of Bre1 couples histone H2B ubiquitination to DNA replication and repair.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  19. Article
  20. Article

51 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

6 authors at 1 institution in 1 country.

Xin XuDepartment of Biochemistry, Vanderbilt University School of Medicine, 613 Light Hall, 23rd at Pierce Avenue, Nashville, TN 37232, USA.
Sivaraja Vaithiyalingam
Gloria G Glick
Daniel A Mordes
Walter J Chazin
David Cortez
Vanderbilt University · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Structural Biology Facility CoreP30ES000267 · NIEHS · VANDERBILT UNIVERSITY · PI GUENGERICH, F PETER · 1985 to 2014
$20.3M
Function of the ATR-ATRIP ComplexR01CA102729 · NCI · VANDERBILT UNIVERSITY · PI CORTEZ, DAVID K · 2003 to 2018
$4.2M
Structural Basis for RPA Functions in DNA ProcessingR01GM065484 · NIGMS · VANDERBILT UNIVERSITY · PI CHAZIN, WALTER J. · 2003 to 2015
$3.9M
NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA102729NIEHS NIH HHS P30 ES000267NIGMS NIH HHS R01 GM065484
6 · The paper itself

Abstract

ATR kinase activation requires the recruitment of the ATR-ATRIP and RAD9-HUS1-RAD1 (9-1-1) checkpoint complexes to sites of DNA damage or replication stress. Replication protein A (RPA) bound to single-stranded DNA is at least part of the molecular recognition element that recruits these checkpoint complexes. We have found that the basic cleft of the RPA70 N-terminal oligonucleotide-oligosaccharide fold (OB-fold) domain is a key determinant of checkpoint activation. This protein-protein interaction surface is able to bind several checkpoint proteins, including ATRIP, RAD9, and MRE11. RAD9 binding to RPA is mediated by an acidic peptide within the C-terminal RAD9 tail that has sequence similarity to the primary RPA-binding surface in the checkpoint recruitment domain (CRD) of ATRIP. Mutation of the RAD9 CRD impairs its localization to sites of DNA damage or replication stress without perturbing its ability to form the 9-1-1 complex or bind the ATR activator TopBP1. Disruption of the RAD9-RPA interaction also impairs ATR signaling to CHK1 and causes hypersensitivity to both DNA damage and replication stress. Thus, the basic cleft of the RPA70 N-terminal OB-fold domain binds multiple checkpoint proteins, including RAD9, to promote ATR signaling.

Indexed as

Adaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsAtaxia Telangiectasia Mutated ProteinsCell CycleCell Cycle ProteinsCell LineDNA-Binding ProteinsDNA DamageDNA ReplicationEnzyme ActivationHumansModels, MolecularMolecular Sequence DataMutationProtein ConformationAdaptor Proteins, Signal TransducingAtaxia Telangiectasia Mutated ProteinsATRIP protein, humanATR protein, humanCell Cycle ProteinsDNA-Binding ProteinsProtein Serine-Threonine Kinasesrad9 proteinReplication Protein ARNA, Small InterferingRPA1 protein, human

Identifiers

PMID18936170
PMCPMC2593429
OpenAlexW2167264368

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.