Evidence map›Paper›PMID 35300981›Full record

ArticleThe Journal of biological chemistry2022

The nuclease activity of DNA2 promotes exonuclease 1-independent mismatch repair.

Lyudmila Y Kadyrova, Basanta K Dahal, Vaibhavi Gujar, James M Daley, Patrick Sung, Farid A Kadyrov

Open access · goldAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 30% 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

13 citing papers in PubMed, 10 citations in OpenAlex.

  1. DNA Repair Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Mechanism of MutLβ-dependent DNA expansions.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. 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

6 authors at 2 institutions in 1 country.

Lyudmila Y KadyrovaDepartment of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, Illinois, USA.
Basanta K DahalDepartment of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, Illinois, USA.
Vaibhavi GujarDepartment of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, Illinois, USA.
James M DaleyDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA.
Patrick SungDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA.
Farid A KadyrovDepartment of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, Illinois, USA. Electronic address: fkadyrov@siumed.edu.
Southern Illinois University School of Medicine · USThe University of Texas Health Science Center at San Antonio · US

Funding

Mechanisms of DNA Homology-directed Genome Repair and Tumor SuppressionR35CA241801 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SUNG, PATRICK · 2019 to 2025
$6.0M
Novel mechanisms in DNA mismatch repairR01GM132128 · NIGMS · SOUTHERN ILLINOIS UNIVERSITY CARBONDALE · PI KADYROV, FARID · 2020 to 2023
$1.2M
NCI NIH HHS R35 CA241801NIGMS NIH HHS R01 GM132128
6 · The paper itself

Abstract

The DNA mismatch repair (MMR) system is a major DNA repair system that corrects DNA replication errors. In eukaryotes, the MMR system functions via mechanisms both dependent on and independent of exonuclease 1 (EXO1), an enzyme that has multiple roles in DNA metabolism. Although the mechanism of EXO1-dependent MMR is well understood, less is known about EXO1-independent MMR. Here, we provide genetic and biochemical evidence that the DNA2 nuclease/helicase has a role in EXO1-independent MMR. Biochemical reactions reconstituted with purified human proteins demonstrated that the nuclease activity of DNA2 promotes an EXO1-independent MMR reaction via a mismatch excision-independent mechanism that involves DNA polymerase δ. We show that DNA polymerase ε is not able to replace DNA polymerase δ in the DNA2-promoted MMR reaction. Unlike its nuclease activity, the helicase activity of DNA2 is dispensable for the ability of the protein to enhance the MMR reaction. Further examination established that DNA2 acts in the EXO1-independent MMR reaction by increasing the strand-displacement activity of DNA polymerase δ. These data reveal a mechanism for EXO1-independent mismatch repair.

Indexed as

DNA HelicasesDNA Mismatch RepairDNA Polymerase IIIExodeoxyribonucleasesHumansDNA2 protein, humanDNA HelicasesDNA Polymerase IIIexodeoxyribonuclease IExodeoxyribonucleases

Identifiers

PMID35300981
PMCPMC9036127
OpenAlexW4220750367

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.