Evidence map›Paper›PMID 25773776›Full record

ArticleMutation research

Deletion of BRCA2 exon 27 causes defects in response to both stalled and collapsed replication forks.

Tae Moon Kim, Mi Young Son, Sherry Dodds, Lingchuan Hu, Paul Hasty

Abstract read
In one paragraph

Article in Mutation research. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
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

21 citing papers in PubMed.

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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

5 authors.

Tae Moon KimDepartment of Molecular Medicine, Institute of Biotechnology, The Barshop Center of Aging, The University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245-3207, USA. Electronic address: kimt@uthscsa.edu.
Mi Young SonDepartment of Molecular Medicine, Institute of Biotechnology, The Barshop Center of Aging, The University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245-3207, USA.
Sherry DoddsDepartment of Molecular Medicine, Institute of Biotechnology, The Barshop Center of Aging, The University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245-3207, USA.
Lingchuan HuDepartment of Molecular Medicine, Institute of Biotechnology, The Barshop Center of Aging, The University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245-3207, USA.
Paul HastyDepartment of Molecular Medicine, Institute of Biotechnology, The Barshop Center of Aging, The University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245-3207, USA. Electronic address: hastye@uthscsa.edu.

Funding

TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Lei Zheng · 1991 to 2026
$59.1M
THE IMPACT OF CELLULAR DEFENSE ON THE ROLE OF Ku80 IN GENOME MAINTENANCE AND LONGP01AG017242 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI VIJG, JAN · 1999 to 2023
$46.1M
Cancer Biology Training ProgramT32CA148724 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Pei Wang, Feng-Chun Yang · 2011 to 2026
$3.3M
How does TREX2 maintain and alter chromosomes?R01CA188032 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HASTY, EDWARD PAUL, MONTAGNA, CRISTINA · 2014 to 2018
$1.8M
Discovering TREX1 and TREX2 Function in Mammalian Cells and MiceR01CA123203 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HASTY, EDWARD PAUL · 2007 to 2011
$1.4M
NCI NIH HHS 1 RO1 CA123203-01A1NCI NIH HHS P30 CA054174NCI NIH HHS R01 CA123203NCI NIH HHS R01 CA188032NCI NIH HHS T32 CA148724NIA NIH HHS 2P01AG017242-12NIA NIH HHS P01 AG017242
6 · The paper itself

Abstract

BRCA2 is a tumor suppressor that maintains genomic integrity through double strand break (DSB) repair and replication fork protection. The BRC motifs and an exon 27-encoded domain (Ex27) of BRCA2 interact with the recombinase RAD51 to, respectively, facilitate the formation and stability of a RAD51 filament on single strand DNA. The BRC-RAD51 associations enable DSB repair while the Ex27-RAD51 association protects the nascent replication strand from MRE11-mediated degradation. MRE11 is a nuclease that facilitates the generation of 3' overhangs needed for homologous recombination (HR)-mediated DSB repair. Here we report the dynamics of replication fork maintenance in mouse embryonic stem (ES) cells deleted for Ex27 (brca2(lex1/lex2)) after exposure to hydroxyurea (HU) that depletes nucleotides. HU conditions were varied from mild to severe. Mild conditions induce an ATR-response to replication fork stalling while severe conditions induce a DNA-PKCS-response to replication fork collapse and a DSB. These responses were differentiated by replication protein A (RPA) phosphorylation. We found that Ex27 deletion reduced MRE11 localization to stalled, but not collapsed, replication forks and that Ex27-deletion caused a proportionately more severe phenotype with HU dose. Therefore, the BRCA2 exon 27 domain maintains chromosomal integrity at both stalled and collapsed replication forks consistent with involvement in both replication fork maintenance and double strand break repair.

Indexed as

Gene DeletionAnimalsBinding SitesBRCA2 ProteinCells, CulturedDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA RepairDNA Repair EnzymesDNA ReplicationExonsGenomic InstabilityHydroxyureaMiceMRE11 Homologue ProteinNucleic Acid Synthesis InhibitorsBRCA2 ProteinBRCA2 protein, mouseDNA-Binding ProteinsDNA Repair EnzymesHydroxyureaMre11a protein, mouseMRE11 Homologue ProteinNucleic Acid Synthesis InhibitorsRad51 protein, mouseRad51 RecombinaseBRCA2Chromosomal instabilityDouble strand breakRAD51Replication fork stalling

Identifiers

PMID25773776
PMCPMC4136705

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Registered trials

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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.