Evidence map›Paper›PMID 33555350›Full record

ArticleNucleic acids research2021

Human Rev1 relies on insert-2 to promote selective binding and accurate replication of stabilized G-quadruplex motifs.

Amit Ketkar, Lane Smith, Callie Johnson, Alyssa Richey, Makayla Berry, Jessica H Hartman, Leena Maddukuri, Megan R Reed, Julie E C Gunderson, Justin W C Leung and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

14 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Sensitization of cancer cells to DNA-damaging agents by expression of the REV1 C-terminal domain: Implications for chemotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Creation and resolution of non-B-DNA structural impediments during replication.Critical reviews in biochemistry and molecular biology · 2022
    Article
  10. Article
  11. Article
  12. Review
  13. G-quadruplex DNA: a novel target for drug design.Cellular and molecular life sciences : CMLS · 2021
    Review
  14. 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

11 authors at 3 institutions in 1 country.

Amit KetkarDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Lane SmithDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Callie JohnsonArkansas School for Mathematics, Sciences, and the Arts, Hot Springs, AR 71901, USA.
Alyssa RicheyArkansas School for Mathematics, Sciences, and the Arts, Hot Springs, AR 71901, USA.
Makayla BerryDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Jessica H HartmanDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Leena MaddukuriDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Megan R ReedDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Julie E C GundersonDepartment of Physics, Hendrix College, Conway, AR 72032, USA.
Justin W C LeungDepartment of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Robert L EoffDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
University of Arkansas for Medical Sciences · USHendrix College · USMedical University of South Carolina · US

Funding

Expanding Translational Research in ArkansasUL1TR003107 · NCATS · UNIV OF ARKANSAS FOR MED SCIS · PI JAMES, LAURA P · 2019 to 2023
$21.6M
The role of SMAD1 and SATB2 in colon patterningP20GM130457 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Thibaut Barnoud · 2020 to 2026
$18.7M
Proteomics CoreP30DK123704 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI DON C. ROCKEY · 2020 to 2026
$8.8M
Deciphering the chromatin-based DNA damage response pathwayR35GM137798 · NIGMS · UNIV OF ARKANSAS FOR MED SCIS · PI Justin Wai Chung Leung · 2020 to 2026
$2.4M
Mechanistic characterization of the cell cycle-dependent DNA repair pathway- ResubmissionR01CA244261 · NCI · UNIV OF ARKANSAS FOR MED SCIS · PI Justin Wai Chung Leung · 2021 to 2026
$1.5M
The role of macroH2A-ZMYM3 in genome stability and tumorigenesisK22CA204354 · NCI · UNIV OF ARKANSAS FOR MED SCIS · PI LEUNG, JUSTIN WAI CHUNG · 2018 to 2020
$538k
NCATS NIH HHS UL1 TR003107NCI NIH HHS K22 CA204354NCI NIH HHS R01 CA244261NIDDK NIH HHS P30 DK123704NIGMS NIH HHS P20 GM130457NIGMS NIH HHS R35 GM137798
6 · The paper itself

Abstract

We previously reported that human Rev1 (hRev1) bound to a parallel-stranded G-quadruplex (G4) from the c-MYC promoter with high affinity. We have extended those results to include other G4 motifs, finding that hRev1 exhibited stronger affinity for parallel-stranded G4 than either anti-parallel or hybrid folds. Amino acids in the αE helix of insert-2 were identified as being important for G4 binding. Mutating E466 and Y470 to alanine selectively perturbed G4 binding affinity. The E466K mutant restored wild-type G4 binding properties. Using a forward mutagenesis assay, we discovered that loss of hRev1 increased G4 mutation frequency >200-fold compared to the control sequence. Base substitutions and deletions occurred around and within the G4 motif. Pyridostatin (PDS) exacerbated this effect, as the mutation frequency increased >700-fold over control and deletions upstream of the G4 site more than doubled. Mutagenic replication of G4 DNA (±PDS) was partially rescued by wild-type and E466K hRev1. The E466A or Y470A mutants failed to suppress the PDS-induced increase in G4 mutation frequency. These findings have implications for the role of insert-2, a motif conserved in vertebrates but not yeast or plants, in Rev1-mediated suppression of mutagenesis during G4 replication.

Indexed as

DNA ReplicationG-QuadruplexesCell LineDNADNA-Directed DNA PolymeraseGenes, mycHumansModels, MolecularMutationNucleotide MotifsNucleotidyltransferasesProtein BindingY-Family DNA PolymerasesDNADNA-Directed DNA PolymeraseNucleotidyltransferasesREV1 protein, humanY-Family DNA Polymerases

Identifiers

PMID33555350
PMCPMC7913688
OpenAlexW3127629541

What OpenQuestion holds

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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.