Evidence map›Paper›PMID 27131385›Full record

ArticleNucleic acids research2016

Dynamic binding of replication protein a is required for DNA repair.

Ran Chen, Shyamal Subramanyam, Adrian H Elcock, Maria Spies, Marc S Wold

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

65 citing papers in PubMed, 100 citations in OpenAlex.

  1. Review
  2. Response Factor Correction for Quantitative Determination of HomooligomericJournal of the American Society for Mass Spectrometry · 2026
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  12. Review
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  14. Fluorescent human RPA to track assembly dynamics on DNA.bioRxiv : the preprint server for biology · 2023
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

5 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.

Ran ChenDepartment of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Shyamal SubramanyamDepartment of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Adrian H ElcockDepartment of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Maria SpiesDepartment of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Marc S WoldDepartment of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA marc-wold@uiowa.edu.
University of Iowa · USUniversity of Illinois Urbana-Champaign · US

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Douglas Robert Spitz · 2000 to 2026
$70.0M
FUNCTIONAL ROLES OF CELLULAR PROTEINS IN DNA REPLICATIONR01GM044721 · NIGMS · UNIVERSITY OF IOWA · PI WOLD, MARC S · 1990 to 2009
$2.2M
Molecular Simulations of Folding & Association in Physiological EnvironmentsR01GM087290 · NIGMS · UNIVERSITY OF IOWA · PI ELCOCK, ADRIAN HAMILTON · 2009 to 2017
$1.6M
Regulation of unwinding and remodeling activities in FeS-DNA helicasesR01GM108617 · NIGMS · UNIVERSITY OF IOWA · PI SPIES, MARIA · 2014 to 2018
$1.6M
NIGMS NIH HHS R01 GM044721NIGMS NIH HHS R01 GM087290NIGMS NIH HHS R01 GM108617
6 · The paper itself

Abstract

Replication protein A (RPA), the major eukaryotic single-stranded DNA (ssDNA) binding protein, is essential for replication, repair and recombination. High-affinity ssDNA-binding by RPA depends on two DNA binding domains in the large subunit of RPA. Mutation of the evolutionarily conserved aromatic residues in these two domains results in a separation-of-function phenotype: aromatic residue mutants support DNA replication but are defective in DNA repair. We used biochemical and single-molecule analyses, and Brownian Dynamics simulations to determine the molecular basis of this phenotype. Our studies demonstrated that RPA binds to ssDNA in at least two modes characterized by different dissociation kinetics. We also showed that the aromatic residues contribute to the formation of the longer-lived state, are required for stable binding to short ssDNA regions and are needed for RPA melting of partially duplex DNA structures. We conclude that stable binding and/or the melting of secondary DNA structures by RPA is required for DNA repair, including RAD51 mediated DNA strand exchange, but is dispensable for DNA replication. It is likely that the binding modes are in equilibrium and reflect dynamics in the RPA-DNA complex. This suggests that dynamic binding of RPA to DNA is necessary for different cellular functions.

Indexed as

DNA RepairDNA ReplicationBinding SitesCloning, MolecularDNA Breaks, Single-StrandedDNA, Single-StrandedEscherichia coliGene ExpressionHumansKineticsMolecular Dynamics SimulationMutationNucleic Acid ConformationNucleic Acid DenaturationProtein BindingProtein Interaction Domains and MotifsDNA, Single-StrandedRAD51 protein, humanRad51 RecombinaseRecombinant Fusion ProteinsReplication Protein ARPA1 protein, human

Identifiers

PMID27131385
PMCPMC4937323
OpenAlexW2342557539

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.