Evidence map›Paper›PMID 30975033›Full record

ArticleCell cycle (Georgetown, Tex.)2019

RPA-coated single-stranded DNA promotes the ETAA1-dependent activation of ATR.

Ke Lyu, Akiko Kumagai, William G Dunphy

Open access · hybridAbstract read
In one paragraph

Article in Cell cycle (Georgetown, Tex.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

11 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. DNA damage responses that enhance resilience to replication stress.Cellular and molecular life sciences : CMLS · 2021
    Review
  9. Review
  10. Article
  11. Roles of OB-Fold Proteins in Replication Stress.Frontiers in cell and developmental biology · 2020
    Review
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

3 authors at 1 institution in 1 country.

Ke Lyua Division of Biology and Biological Engineering , California Institute of Technology , Pasadena , CA , USA.ORCID 0000-0002-2483-2253
Akiko Kumagaia Division of Biology and Biological Engineering , California Institute of Technology , Pasadena , CA , USA.ORCID 0000-0003-2422-8053
William G Dunphya Division of Biology and Biological Engineering , California Institute of Technology , Pasadena , CA , USA.ORCID 0000-0001-7598-8939
California Institute of Technology · US

Funding

Role of ATR in Cell Cycle CheckpointsR01GM070891 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI DUNPHY, WILLIAM G · 2004 to 2018
$5.7M
ENZYMOLOGY OF MITOSIS PROMOTING FACTOR (MPF)R01GM043974 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI DUNPHY, WILLIAM G · 1990 to 2022
$4.0M
Enzymology of Mitosis Promoting Factor (MPF)R37GM043974 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI DUNPHY, WILLIAM G · 2002 to 2011
$4.0M
NIGMS NIH HHS R01 GM043974NIGMS NIH HHS R01 GM070891NIGMS NIH HHS R37 GM043974
6 · The paper itself

Abstract

Besides TopBP1, ETAA1 has been identified more recently as an activator of the ATR-ATRIP complex in human cells. We have examined the role of ETAA1 in the Xenopus egg-extract system, which has been instrumental in the study of ATR-ATRIP. Depletion of ETAA1 from egg extracts did not noticeably reduce the activation of ATR-ATRIP in response to replication stress, as monitored by the ATR-dependent phosphorylation of Chk1 and RPA. Moreover, lack of ETAA1 did not appear to affect DNA replication during an unperturbed S-phase. Significantly, we find that TopBP1 is considerably more abundant than ETAA1 in egg extracts. We proceeded to show that ETAA1 could support the activation of ATR-ATRIP in response to replication stress if we increased its concentration in egg extracts by adding extra full-length recombinant ETAA1. Thus, TopBP1 appears to be the predominant activator of ATR-ATRIP in response to replication stress in this system. We have also explored the biochemical mechanism by which ETAA1 activates ATR-ATRIP. We have developed an in vitro system in which full-length recombinant ETAA1 supports activation of ATR-ATRIP in the presence of defined components. We find that binding of ETAA1 to RPA associated with single-stranded DNA (ssDNA) greatly stimulates its ability to activate ATR-ATRIP. Thus, RPA-coated ssDNA serves as a direct positive effector in the ETAA1-mediated activation of ATR-ATRIP.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsAntibodiesAntigens, SurfaceAtaxia Telangiectasia Mutated ProteinsCheckpoint Kinase 1ChromatinDNA-Binding ProteinsDNA ReplicationDNA, Single-StrandedPhosphorylationProtein BindingRecombinant ProteinsReplication Protein AS PhaseXenopusAdaptor Proteins, Signal TransducingAntibodiesAntigens, SurfaceAtaxia Telangiectasia Mutated ProteinsAtr protein, XenopusCheckpoint Kinase 1Chek1 protein, XenopusChromatinDNA-Binding ProteinsDNA, Single-StrandedRecombinant ProteinsReplication Protein ATopBP1 protein, XenopusXenopus ProteinsATRATRIPChk1egg extractETAA1RPATopBP1

Identifiers

PMID30975033
PMCPMC6527274
OpenAlexW2938493052

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.