Evidence map›Paper›PMID 24608368›Full record

ArticleNature structural & molecular biology2014

RPA antagonizes microhomology-mediated repair of DNA double-strand breaks.

Sarah K Deng, Bryan Gibb, Mariana Justino de Almeida, Eric C Greene, Lorraine S Symington

Open access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.

0numbers the graph read from it
0cells of the map it votes in
143citing papers in PubMed
10.2field-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

143 citing papers in PubMed, 220 citations in OpenAlex.

  1. DNA Repair Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
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  10. Coordinated transfer of DNA between Pol θ and Pol δ resets microhomology choice during double-strand break repair.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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  14. Review
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83 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Sarah K DengDepartment of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Bryan GibbDepartment of Biochemistry and Biophysics, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Mariana Justino de AlmeidaDepartment of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Eric C Greene1] Department of Biochemistry and Biophysics, Columbia University College of Physicians and Surgeons, New York, New York, USA. [2] Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Lorraine S SymingtonDepartment of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Columbia University · US

Funding

The Role of CTIP in Lymphocyte Development and LymphomagenesisP01CA174653 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI RABADAN, RAUL · 2014 to 2024
$17.6M
Mechanisms of Homologous Recombination in YeastR01GM041784 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI SYMINGTON, LORRAINE S · 1989 to 2017
$7.8M
CELL, MOLECULAR AND DEVELOPMENTAL BIOLOGY OF CANCERT32CA009503 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI GAUTIER, JEAN · 1985 to 2016
$6.8M
Elucidating the Mechanisms of DNA RecombinationR01GM074739 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GREENE, ERIC C · 2006 to 2015
$2.7M
Break-induced replication and genome rearrangementsR01GM094386 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SYMINGTON, LORRAINE S · 2010 to 2017
$2.4M
Howard Hughes Medical InstituteNCI NIH HHS P01 CA174653NCI NIH HHS T32 CA009503NIGMS NIH HHS R01 GM041784NIGMS NIH HHS R01 GM074739NIGMS NIH HHS R01 GM094386
6 · The paper itself

Abstract

Microhomology-mediated end joining (MMEJ) is a Ku- and ligase IV-independent mechanism for the repair of DNA double-strand breaks that contributes to chromosome rearrangements. Here we used a chromosomal end-joining assay to determine the genetic requirements for MMEJ in Saccharomyces cerevisiae. We found that end resection influences the ability to expose microhomologies; however, it is not rate limiting for MMEJ in wild-type cells. The frequency of MMEJ increased by up to 350-fold in rfa1 hypomorphic mutants, suggesting that replication protein A (RPA) bound to the single-stranded DNA (ssDNA) overhangs formed by resection prevents spontaneous annealing between microhomologies. In vitro, the mutant RPA complexes were unable to fully extend ssDNA and were compromised in their ability to prevent spontaneous annealing. We propose that the helix-destabilizing activity of RPA channels ssDNA intermediates from mutagenic MMEJ to error-free homologous recombination, thus preserving genome integrity.

Indexed as

DNA Breaks, Double-StrandedDNA End-Joining RepairDNA, Single-StrandedHomologous RecombinationReplication Protein ARNA Polymerase ISaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsDNA, Single-StrandedReplication Protein ARFA1 protein, S cerevisiaeRFA2 protein, S cerevisiaeRNA Polymerase IRPA14 protein, S cerevisiaeSaccharomyces cerevisiae Proteins

Identifiers

PMID24608368
PMCPMC3980576
OpenAlexW2036685117

What OpenQuestion holds

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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.