Evidence map›Paper›PMID 22318518›Full record

ArticleNature2012

Single-molecule imaging of DNA pairing by RecA reveals a three-dimensional homology search.

Anthony L Forget, Stephen C Kowalczykowski

Abstract read
In one paragraph

Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.

0numbers the graph read from it
0cells of the map it votes in
123citing papers in PubMed
10.1field-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

123 citing papers in PubMed, 215 citations in OpenAlex.

  1. Review
  2. Mechanisms That Govern Recombinase Fidelity Control During Eukaryotic Homologous Recombination.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  3. Chromosome topology gates productive RecA homology search.bioRxiv : the preprint server for biology · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. HOP2-MND1 chaperones a diffusing DMC1-ssDNA complex to survey dsDNA for homology recognition during meiotic recombination.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. NProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

63 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

2 authors at 1 institution in 1 country.

Anthony L ForgetDepartment of Microbiology, University of California, Davis, California 95616-8665, USA.
Stephen C Kowalczykowski
University of California, Davis · US

Funding

Mechanistic Studies of Genetic RecombinationR01GM062653 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KOWALCZYKOWSKI, STEPHEN CHARLES · 2010 to 2018
$4.4M
Single-Molecule Assembly of Protein-DNA ComplexesR01GM064745 · NIGMS · UNIVERSITY OF CALIFORNIA DAVIS · PI KOWALCZYKOWSKI, STEPHEN CHARLES · 2002 to 2018
$4.3M
MECHANISTIC STUDIES OF GENETIC RECOMBINATIONR37GM062653 · NIGMS · UNIVERSITY OF CALIFORNIA DAVIS · PI KOWALCZYKOWSKI, STEPHEN CHARLES · 2000 to 2009
$3.6M
NIGMS NIH HHS GM-62653NIGMS NIH HHS GM-64745NIGMS NIH HHS R01 GM062653NIGMS NIH HHS R01 GM064745NIGMS NIH HHS R37 GM062653
6 · The paper itself

Abstract

DNA breaks can be repaired with high fidelity by homologous recombination. A ubiquitous protein that is essential for this DNA template-directed repair is RecA. After resection of broken DNA to produce single-stranded DNA (ssDNA), RecA assembles on this ssDNA into a filament with the unique capacity to search and find DNA sequences in double-stranded DNA (dsDNA) that are homologous to the ssDNA. This homology search is vital to recombinational DNA repair, and results in homologous pairing and exchange of DNA strands. Homologous pairing involves DNA sequence-specific target location by the RecA-ssDNA complex. Despite decades of study, the mechanism of this enigmatic search process remains unknown. RecA is a DNA-dependent ATPase, but ATP hydrolysis is not required for DNA pairing and strand exchange, eliminating active search processes. Using dual optical trapping to manipulate DNA, and single-molecule fluorescence microscopy to image DNA pairing, we demonstrate that both the three-dimensional conformational state of the dsDNA target and the length of the homologous RecA-ssDNA filament have important roles in the homology search. We discovered that as the end-to-end distance of the target dsDNA molecule is increased, constraining the available three-dimensional (3D) conformations of the molecule, the rate of homologous pairing decreases. Conversely, when the length of the ssDNA in the nucleoprotein filament is increased, homology is found faster. We propose a model for the DNA homology search process termed 'intersegmental contact sampling', in which the intrinsic multivalent nature of the RecA nucleoprotein filament is used to search DNA sequence space within 3D domains of DNA, exploiting multiple weak contacts to rapidly search for homology. Our findings highlight the importance of the 3D conformational dynamics of DNA, reveal a previously unknown facet of the homology search, and provide insight into the mechanism of DNA target location by this member of a universal family of proteins.

Indexed as

Base PairingSequence Homology, Nucleic AcidAdenosine TriphosphateBacteriophage lambdaDNA-Binding ProteinsDNA, Single-StrandedDNA, ViralHomologous RecombinationMicroscopy, FluorescenceRec A RecombinasesRecombinational DNA RepairAdenosine TriphosphateDNA-Binding ProteinsDNA, Single-StrandedDNA, ViralRec A Recombinases

Identifiers

PMID22318518
PMCPMC3288143
OpenAlexW2021955395

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.