Evidence map›Paper›PMID 36529288›Full record

ArticleThe Journal of biological chemistry2023

The MRN complex and topoisomerase IIIa-RMI1/2 synchronize DNA resection motor proteins.

Michael M Soniat, Giaochau Nguyen, Hung-Che Kuo, Ilya J Finkelstein

Open access · goldAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

9 citing papers in PubMed, 14 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

4 authors at 1 institution in 1 country.

Michael M SoniatDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, USA; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, USA. Electronic address: msoniat@utexas.edu.
Giaochau NguyenDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, USA; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, USA.
Hung-Che KuoDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, USA; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, USA.
Ilya J FinkelsteinDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, USA; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, USA. Electronic address: ilya@finkelsteinlab.org.
The University of Texas at Austin · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI WALTER J. CHAZIN · 2001 to 2026
$89.6M
Mechanistic Characterization of the First Steps of Human DNA Break RepairR01GM120554 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI FINKELSTEIN, ILYA J · 2016 to 2020
$1.5M
NCI NIH HHS P01 CA092584NIGMS NIH HHS R01 GM120554
6 · The paper itself

Abstract

DNA resection-the nucleolytic processing of broken DNA ends-is the first step of homologous recombination. Resection is catalyzed by the resectosome, a multienzyme complex that includes bloom syndrome helicase (BLM), DNA2 or exonuclease 1 nucleases, and additional DNA-binding proteins. Although the molecular players have been known for over a decade, how the individual proteins work together to regulate DNA resection remains unknown. Using single-molecule imaging, we characterized the roles of the MRE11-RAD50-NBS1 complex (MRN) and topoisomerase IIIa (TOP3A)-RMI1/2 during long-range DNA resection. BLM partners with TOP3A-RMI1/2 to form the BTRR (BLM-TOP3A-RMI1/2) complex (or BLM dissolvasome). We determined that TOP3A-RMI1/2 aids BLM in initiating DNA unwinding, and along with MRN, stimulates DNA2-mediated resection. Furthermore, we found that MRN promotes the association between BTRR and DNA and synchronizes BLM and DNA2 translocation to prevent BLM from pausing during resection. Together, this work provides direct observation of how MRN and DNA2 harness the BTRR complex to resect DNA efficiently and how TOP3A-RMI1/2 regulates the helicase activity of BLM to promote efficient DNA repair.

Indexed as

DNADNA RepairDNA Topoisomerases, Type IMultienzyme ComplexesAcid Anhydride HydrolasesCell Cycle ProteinsDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA HelicasesHumansMRE11 Homologue ProteinNuclear ProteinsRecQ HelicasesSingle Molecule ImagingAcid Anhydride HydrolasesBloom syndrome proteinCell Cycle ProteinsDNADNA2 protein, humanDNA-Binding ProteinsDNA HelicasesDNA Topoisomerases, Type IMRE11 Homologue ProteinMRE11 protein, humanMultienzyme ComplexesNBN protein, humanNuclear ProteinsRAD50 protein, humanRecQ HelicasesRMI1 protein, humanRMI2 protein, humanTOP3A protein, humanBLMDNA2DNA curtainsDNA resectiondouble-strand breaksingle molecule

Identifiers

PMID36529288
PMCPMC9971906
OpenAlexW4311770466

What OpenQuestion holds

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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.