Evidence map›Paper›PMID 27596592›Full record

ArticleNucleic acids research2016

High-resolution structure of the presynaptic RAD51 filament on single-stranded DNA by electron cryo-microscopy.

Judith M Short, Yang Liu, Shaoxia Chen, Neelesh Soni, Mallur S Madhusudhan, Mahmud K K Shivji, Ashok R Venkitaraman

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 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
6.8field-weighted citation impact, top 3% 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

64 citing papers in PubMed, 102 citations in OpenAlex.

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4 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

7 authors at 3 institutions in 1 country.

Judith M ShortMedical Research Council Cancer Unit, University of Cambridge, Hills Road, Cambridge CB2 0XZ, UK.
Yang LiuMedical Research Council Cancer Unit, University of Cambridge, Hills Road, Cambridge CB2 0XZ, UK.
Shaoxia ChenMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Neelesh SoniIndian Institute of Science, Education & Research, Dr Homi Babha Road, Pune 411 008, India.
Mallur S MadhusudhanIndian Institute of Science, Education & Research, Dr Homi Babha Road, Pune 411 008, India.
Mahmud K K ShivjiMedical Research Council Cancer Unit, University of Cambridge, Hills Road, Cambridge CB2 0XZ, UK.
Ashok R VenkitaramanMedical Research Council Cancer Unit, University of Cambridge, Hills Road, Cambridge CB2 0XZ, UK arv22@mrc-cu.cam.ac.uk.
University of Cambridge · GBMedical Research Council · GBMRC Laboratory of Molecular Biology · GB

Funding

Medical Research Council G1001522Medical Research Council MC_U105184322Medical Research Council MC_UU_12022/1Medical Research Council MC_UU_12022/8
6 · The paper itself

Abstract

Homologous DNA recombination (HR) by the RAD51 recombinase enables error-free DNA break repair. To execute HR, RAD51 first forms a presynaptic filament on single-stranded (ss) DNA, which catalyses pairing with homologous double-stranded (ds) DNA. Here, we report a structure for the presynaptic human RAD51 filament at 3.5-5.0Å resolution using electron cryo-microscopy. RAD51 encases ssDNA in a helical filament of 103Å pitch, comprising 6.4 protomers per turn, with a rise of 16.1Å and a twist of 56.2°. Inter-protomer distance correlates with rotation of an α-helical region in the core catalytic domain that is juxtaposed to ssDNA, suggesting how the RAD51-DNA interaction modulates protomer spacing and filament pitch. We map Fanconi anaemia-like disease-associated RAD51 mutations, clarifying potential phenotypes. We predict binding sites on the presynaptic filament for two modules present in each BRC repeat of the BRCA2 tumour suppressor, a critical HR mediator. Structural modelling suggests that changes in filament pitch mask or expose one binding site with filament-inhibitory potential, rationalizing the paradoxical ability of the BRC repeats to either stabilize or inhibit filament formation at different steps during HR. Collectively, our findings provide fresh insight into the structural mechanism of HR and its dysregulation in human disease.

Indexed as

Cryoelectron MicroscopyAdenosine DiphosphateBinding SitesBRCA2 ProteinDNA, Single-StrandedGenetic Predisposition to DiseaseHomologous RecombinationHumansModels, MolecularMolecular ConformationMutationProtein BindingProtein Interaction Domains and MotifsProtein SubunitsRad51 RecombinaseRec A RecombinasesAdenosine DiphosphateBRCA2 ProteinDNA, Single-StrandedProtein SubunitsRad51 RecombinaseRec A Recombinases

Identifiers

PMID27596592
PMCPMC5100573
OpenAlexW2515277705

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.