Evidence map›Paper›PMID 25765654›Full record

ArticleNucleic acids research2015

RAD54 family translocases counter genotoxic effects of RAD51 in human tumor cells.

Jennifer M Mason, Kritika Dusad, William Douglass Wright, Jennifer Grubb, Brian Budke, Wolf-Dietrich Heyer, Philip P Connell, Ralph R Weichselbaum, Douglas K Bishop

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

56 citing papers in PubMed, 87 citations in OpenAlex.

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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

9 authors at 2 institutions in 1 country.

Jennifer M MasonDepartment of Radiation and Cellular Oncology, University of Chicago, Cummings Life Science Center, Box 13, 920 East 58th St., Chicago, IL 60637, USA.
Kritika DusadDepartment of Radiation and Cellular Oncology, University of Chicago, Cummings Life Science Center, Box 13, 920 East 58th St., Chicago, IL 60637, USA.
William Douglass WrightDepartment of Molecular and Cellular Biology, University of California, Davis, Davis CA 95616, USA.
Jennifer GrubbDepartment of Radiation and Cellular Oncology, University of Chicago, Cummings Life Science Center, Box 13, 920 East 58th St., Chicago, IL 60637, USA.
Brian BudkeDepartment of Radiation and Cellular Oncology, University of Chicago, Cummings Life Science Center, Box 13, 920 East 58th St., Chicago, IL 60637, USA.
Wolf-Dietrich HeyerDepartment of Molecular and Cellular Biology, University of California, Davis, Davis CA 95616, USA Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
Philip P ConnellDepartment of Radiation and Cellular Oncology, University of Chicago, Cummings Life Science Center, Box 13, 920 East 58th St., Chicago, IL 60637, USA.
Ralph R WeichselbaumDepartment of Radiation and Cellular Oncology, University of Chicago, Cummings Life Science Center, Box 13, 920 East 58th St., Chicago, IL 60637, USA.
Douglas K BishopDepartment of Radiation and Cellular Oncology, University of Chicago, Cummings Life Science Center, Box 13, 920 East 58th St., Chicago, IL 60637, USA Department of Microbiology and Molecular Genetics, University of California, Davis, Davis CA 95616, USA dbishop@uchicago.edu.
University of Chicago · USUniversity of California, Davis · US

Funding

Multi-Disciplinary Training Grant in Cancer ResearchT32CA009594 · NCI · UNIVERSITY OF CHICAGO · PI KAY F MACLEOD, Scott A. Oakes · 1989 to 2026
$11.5M
MEIOTIC INTERACTIONS TO THE RECA HOMOLOGUE DMC1R01GM050936 · NIGMS · UNIVERSITY OF CHICAGO · PI BISHOP, DOUGLAS K · 1994 to 2019
$9.2M
RECOMBINATIONAL MECHANISMS OF DNA REPAIR IN EUKARYOTESR01GM058015 · NIGMS · UNIVERSITY OF CALIFORNIA DAVIS · PI HEYER, WOLF-DIETRICH · 2000 to 2025
$8.8M
RAD51 Inhibitors for Chemotherapy and Radiation TherapyR01CA142642 · NCI · UNIVERSITY OF CHICAGO · PI CONNELL, PHILIP P · 2010 to 2019
$4.8M
NCI NIH HHS 5T32CA009594NCI NIH HHS CA142642-02NCI NIH HHS R01 CA142642NIGMS NIH HHS GM50936NIGMS NIH HHS GM58015NIGMS NIH HHS R01 GM050936NIGMS NIH HHS R01 GM058015
6 · The paper itself

Abstract

The RAD54 family DNA translocases have several biochemical activities. One activity, demonstrated previously for the budding yeast translocases, is ATPase-dependent disruption of RAD51-dsDNA binding. This activity is thought to promote dissociation of RAD51 from heteroduplex DNA following strand exchange during homologous recombination. In addition, previous experiments in budding yeast have shown that the same activity of Rad54 removes Rad51 from undamaged sites on chromosomes; mutants lacking Rad54 accumulate nonrepair-associated complexes that can block growth and lead to chromosome loss. Here, we show that human RAD54 also promotes the dissociation of RAD51 from dsDNA and not ssDNA. We also show that translocase depletion in tumor cell lines leads to the accumulation of RAD51 on chromosomes, forming complexes that are not associated with markers of DNA damage. We further show that combined depletion of RAD54L and RAD54B and/or artificial induction of RAD51 overexpression blocks replication and promotes chromosome segregation defects. These results support a model in which RAD54L and RAD54B counteract genome-destabilizing effects of direct binding of RAD51 to dsDNA in human tumor cells. Thus, in addition to having genome-stabilizing DNA repair activity, human RAD51 has genome-destabilizing activity when expressed at high levels, as is the case in many human tumors.

Indexed as

DNA RepairCell Line, TumorCell ProliferationDNA-Binding ProteinsDNA HelicasesDNA, NeoplasmHumansMCF-7 CellsMultiprotein ComplexesMutagensNeoplasmsNuclear ProteinsRad51 RecombinaseReplication Protein ARNA, Small InterferingDNA-Binding ProteinsDNA HelicasesDNA, NeoplasmMultiprotein ComplexesMutagensNuclear ProteinsRAD51 protein, humanRad51 RecombinaseRAD54B protein, humanRAD54L protein, humanReplication Protein ARNA, Small InterferingRPA1 protein, human

Identifiers

PMID25765654
PMCPMC4381078
OpenAlexW2166510365

What OpenQuestion holds

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LicenceCC BY
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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.