Evidence map›Paper›PMID 42670257›Full record

ArticleNucleic acids research2026

Fluorescent reporter assay reveals ribonucleotides promote mismatch correction in vivo.

Sophie Erlich, Patrizia Mazzucato, Daniel J Laverty, Leona D Samson, Zachary D Nagel

Abstract read
In one paragraph

Article in Nucleic acids research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Sophie ErlichDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States.
Patrizia MazzucatoDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Daniel J LavertyDepartment of Chemistry, Lehigh University, Bethlehem, PA 18018, United States.ORCID 0000-0003-4529-2302
Leona D SamsonDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Zachary D NagelDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States.ORCID 0000-0003-2104-2093

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Multi-Pathway DNA Repair Capacity Measurements in Lung Cancer Patients and Healthy ControlsU01ES029520 · NIEHS · HARVARD SCHOOL OF PUBLIC HEALTH · PI CHRISTIANI, DAVID C, ENGELWARD, BEVIN P. · 2018 to 2022
$3.3M
Developing novel methods to measure DNA repair capacity in human populationsDP1OD006422 · OD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SAMSON, LEONA D. · 2009 to 2011
$2.5M
NCI NIH HHS P01 CA092584NIEHS NIH HHS U01 ES029520NIH HHS DP1 OD006422NIH HHS DP1OD006422NIH HHS P01CA092584NIH HHS U01ES029520
6 · The paper itself

Abstract

Ribonucleotides can serve as a strand discrimination signal in reconstituted in vitro biochemical mismatch repair (MMR) assays, but the influence of ribonucleotides on mismatch correction has not been measured directly in vivo. We have developed a fluorescence-based host cell reactivation assay that reports correction of a mismatch in proximity of a site-specifically incorporated ribonucleotide. A ribonucleotide leads to enhanced mismatch correction. While neither inactivation of a single allele nor knockdown of RNaseH2 is sufficient to suppress ribonucleotide directed MMR, a modest but statistically significant impairment for repair of mismatches in the presence of an embedded ribonucleotide is observed in RNaseH2 knockout cell lines. Reporter plasmids with ribonucleotides located in either the 3' or 5' orientation are robustly repaired in MMR-proficient cells but are weakly repaired in MMR-deficient cells, underscoring their utility as effective MMR reporters. Significant ribonucleotide-enhanced mismatch correction was consistently observed in MMR-deficient cells when the ribonucleotide is in the 3' orientation. The presence of a ribonucleotide led to enhanced MMR even in RNaseH2 knockout cells, suggesting that other enzymes may promote ribonucleotide-directed MMR. Loss of RNaseH2 was not sufficient to confer significant resistance to the alkylating agent, temozolomide, in support of a model in which ribonucleotide-directed repair events make minor contributions to the canonical MMR pathway in mammalian cells. We propose a model in which MMR-independent ribonucleotide enhanced correction of mismatches can proceed by ribonucleotide excision repair when the ribonucleotide is in the 5' direction, and proceeds by an unknown mechanism when the ribonucleotide is in the 3' direction.

Indexed as

DNA Mismatch RepairRibonucleotidesBase Pair MismatchCell LineGenes, ReporterHumansMutS Homolog 2 ProteinRibonuclease HMutS Homolog 2 ProteinRibonuclease HRibonucleotides

Identifiers

PMID42670257
PMCPMC13527164

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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.