Evidence map›Paper›PMID 37526271›Full record

ArticleNucleic acids research2023

FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability.

Wenpeng Liu, Piotr Polaczek, Ivan Roubal, Yuan Meng, Won-Chae Choe, Marie-Christine Caron, Carl A Sedgeman, Yu Xi, Changwei Liu, Qiong Wu and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  11. TCAF1 promotes TRPV2-mediated CaNature communications · 2024
    Article
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  13. Review
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  17. Ubiquitin and SUMO pathways in DNA replication and replication-coupled repair.Critical reviews in biochemistry and molecular biology
    Review
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

14 authors at 4 institutions in 3 countries.

Wenpeng LiuBraun Laboratories, California Institute of Technology, Pasadena, CA 91125, USA.
Piotr PolaczekBraun Laboratories, California Institute of Technology, Pasadena, CA 91125, USA.
Ivan RoubalBraun Laboratories, California Institute of Technology, Pasadena, CA 91125, USA.
Yuan MengDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, 1500 East Duarte Road, Duarte, CA 91010-3000, USA.
Won-Chae ChoeBraun Laboratories, California Institute of Technology, Pasadena, CA 91125, USA.
Marie-Christine CaronGenome Stability Laboratory, CHU de Québec Research Center, HDQ Pavilion, Oncology Division, 9 McMahon, Québec City, QC G1R 3S3, Canada.
Carl A SedgemanBraun Laboratories, California Institute of Technology, Pasadena, CA 91125, USA.
Yu XiColleges of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310027, China.
Changwei LiuDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, 1500 East Duarte Road, Duarte, CA 91010-3000, USA.
Qiong WuDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, 1500 East Duarte Road, Duarte, CA 91010-3000, USA.
Li ZhengDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, 1500 East Duarte Road, Duarte, CA 91010-3000, USA.ORCID 0000-0002-3744-185X
Jean-Yves MassonGenome Stability Laboratory, CHU de Québec Research Center, HDQ Pavilion, Oncology Division, 9 McMahon, Québec City, QC G1R 3S3, Canada.ORCID 0000-0002-4403-7169
Binghui ShenDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, 1500 East Duarte Road, Duarte, CA 91010-3000, USA.ORCID 0000-0002-4408-407X
Judith L CampbellBraun Laboratories, California Institute of Technology, Pasadena, CA 91125, USA.ORCID 0000-0001-8291-5551
California Institute of Technology · USCity of Hope · USUniversité Laval · CAZhejiang University · CN

Funding

Role of Nucleases in RNA Primer Removal and MutagenesisR01CA085344 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI SHEN, BINGHUI · 1999 to 2024
$7.7M
DNA repair gene mutations and prostate cancerR01CA233664 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI SHEN, BINGHUI, SUN, ZIJIE · 2020 to 2024
$3.4M
Functional Analysis of Structure Specific Nucleases in Genome Stability and CancersR50CA211397 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI ZHENG, LI · 2016 to 2025
$3.3M
Role of DNA Replication Stress in Genome Instability and CancerR01GM123554 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI CAMPBELL, JUDITH L · 2017 to 2020
$1.2M
NCI NIH HHS R01 CA085344NCI NIH HHS R01 CA233664NCI NIH HHS R50 CA211397NIGMS NIH HHS R01 GM123554
6 · The paper itself

Abstract

FANCD2 protein, a key coordinator and effector of the interstrand crosslink repair pathway, is also required to prevent excessive nascent strand degradation at hydroxyurea-induced stalled forks. The RAD51 recombinase has also been implicated in regulation of resection at stalled replication forks. The mechanistic contributions of these proteins to fork protection are not well understood. Here, we used purified FANCD2 and RAD51 to study how each protein regulates DNA resection at stalled forks. We characterized three mechanisms of FANCD2-mediated fork protection: (1) The N-terminal domain of FANCD2 inhibits the essential DNA2 nuclease activity by directly binding to DNA2 accounting for over-resection in FANCD2 defective cells. (2) Independent of dimerization with FANCI, FANCD2 itself stabilizes RAD51 filaments to inhibit multiple nucleases, including DNA2, MRE11 and EXO1. (3) Unexpectedly, we uncovered a new FANCD2 function: by stabilizing RAD51 filaments, FANCD2 acts to stimulate the strand exchange activity of RAD51. Our work biochemically explains non-canonical mechanisms by which FANCD2 and RAD51 protect stalled forks. We propose a model in which the strand exchange activity of FANCD2 provides a simple molecular explanation for genetic interactions between FANCD2 and BRCA2 in the FA/BRCA fork protection pathway.

Indexed as

DNA HelicasesDNA ReplicationRad51 RecombinaseDNA RepairFanconi Anemia Complementation Group D2 ProteinGenomic InstabilityHumansDNA2 protein, humanDNA HelicasesFANCD2 protein, humanFanconi Anemia Complementation Group D2 ProteinRAD51 protein, humanRad51 Recombinase

Identifiers

PMID37526271
PMCPMC10516637
OpenAlexW4385441933

What Socratic 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 Socratic graph.