ArticleMolecular cell2012
RNase H and postreplication repair protect cells from ribonucleotides incorporated in DNA.
Article in Molecular cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 171 citations in OpenAlex.
- DNA polymerase I and DnaE mediate RNA-templated DNA synthesis over embedded ribonucleotides.Nucleic acids research · 2026Article
- Ubiquitin degradation of the Ribonuclease H2 subunit B Rnh2B regulates the virulence ofVirulence · 2025Article
- Genome-wide ribonucleotide detection in Archaea.Nucleic acids research · 2025Article
- Decoding nucleoside supplementation: how thymidine outperforms ribonucleosides in accelerating mammalian replication forks.Nucleic acids research · 2025Article
- RNA transcripts serve as a template for double-strand break repair in human cells.Nature communications · 2025Article
- The Smc5/6 complex counteracts R-loop formation at highly transcribed genes in cooperation with RNase H2.eLife · 2024Article
- Distinct features of ribonucleotides within genomic DNA in Aicardi-Goutières syndrome ortholog mutants ofiScience · 2024Article
- Detection of ribonucleotides embedded in DNA by Nanopore sequencing.Communications biology · 2024Article
- RNase H2 degrades toxic RNA:DNA hybrids behind stalled forks to promote replication restart.The EMBO journal · 2023Article
- How RNA impacts DNA repair.DNA repair · 2023Review
- Distinct features of ribonucleotides within genomic DNA in Aicardi-Goutières syndrome (AGS)-ortholog mutants ofbioRxiv : the preprint server for biology · 2023Article
- Ribonucleotide and R-Loop Damage in Plastid DNA and Mitochondrial DNA during Maize Development.Plants (Basel, Switzerland) · 2023Article
- Genetic requirements for repair of lesions caused by single genomic ribonucleotides in S phase.Nature communications · 2023Article
- CRISPR/Cas9-mediated targeted knock-in of large constructs using nocodazole and RNase HII.Scientific reports · 2023Article
- Mechanistic investigation of human maturation of Okazaki fragments reveals slow kinetics.Nature communications · 2022Article
- Ribonucleotide Incorporation by Eukaryotic B-Family Replicases and Its Implications for Genome Stability.Annual review of biochemistry · 2022Review
- The catalytic mechanism, metal dependence, substrate specificity, and biodiversity of ribonuclease H.Frontiers in microbiology · 2022Review
- VID22 counteracts G-quadruplex-induced genome instability.Nucleic acids research · 2021Article
- A role for Rad5 in ribonucleoside monophosphate (rNMP) tolerance.Life science alliance · 2021Article
- Review
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
The chemical identity and integrity of the genome is challenged by the incorporation of ribonucleoside triphosphates (rNTPs) in place of deoxyribonucleoside triphosphates (dNTPs) during replication. Misincorporation is limited by the selectivity of DNA replicases. We show that accumulation of ribonucleoside monophosphates (rNMPs) in the genome causes replication stress and has toxic consequences, particularly in the absence of RNase H1 and RNase H2, which remove rNMPs. We demonstrate that postreplication repair (PRR) pathways-MMS2-dependent template switch and Pol ζ-dependent bypass-are crucial for tolerating the presence of rNMPs in the chromosomes; indeed, we show that Pol ζ efficiently replicates over 1-4 rNMPs. Moreover, cells lacking RNase H accumulate mono- and polyubiquitylated PCNA and have a constitutively activated PRR. Our findings describe a crucial function for RNase H1, RNase H2, template switch, and translesion DNA synthesis in overcoming rNTPs misincorporated during DNA replication, and may be relevant for the pathogenesis of Aicardi-Goutières syndrome.
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Registered trials
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.