ArticleHuman molecular genetics2015
Reduction of hRNase H2 activity in Aicardi-Goutières syndrome cells leads to replication stress and genome instability.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Synthetic lethal mutants inJournal of bacteriology · 2023Pooled it
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Emerging roles of RNA:DNA hybrid regulation by mammalian ribonuclease H2 in replication stress and cancer.Journal of cell science · 2025Review
- Genome-wide ribonucleotide detection in Archaea.Nucleic acids research · 2025Article
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- Human RNase H2 upregulation counteracts oncogene- and chemotherapy-induced replication stress.Oncogene · 2025Article
- Endogenous Ribonucleases: Therapeutic Targeting of the Transcriptome Through Oligonucleotide-Triggered RNA Inactivation.Biomolecules · 2025Review
- A case of severe Aicardi-Goutières syndrome with a homozygous RNASEH2B intronic variant.Human genome variation · 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
- Processing of matched and mismatched rNMPs in DNA by archaeal ribonucleotide excision repair.iScience · 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
- Genetic requirements for repair of lesions caused by single genomic ribonucleotides in S phase.Nature communications · 2023Article
- Mechanistic investigation of human maturation of Okazaki fragments reveals slow kinetics.Nature communications · 2022Article
- RNase H2, mutated in Aicardi-Goutières syndrome, resolves co-transcriptional R-loops to prevent DNA breaks and inflammation.Nature communications · 2022Article
- Transcription-Replication Collisions-A Series of Unfortunate Events.Biomolecules · 2021Review
- Evaluation of repair activity by quantification of ribonucleotides in the genome.Genes to cells : devoted to molecular & cellular mechanisms · 2021Article
- Mechanisms of damage tolerance and repair during DNA replication.Nucleic acids research · 2021Review
- Ribonucleotide incorporation into DNA during DNA replication and its consequences.Critical reviews in biochemistry and molecular biology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Aicardi-Goutières syndrome (AGS) is an inflammatory encephalopathy caused by defective nucleic acids metabolism. Over 50% of AGS mutations affect RNase H2 the only enzyme able to remove single ribonucleotide-monophosphates (rNMPs) embedded in DNA. Ribonucleotide triphosphates (rNTPs) are incorporated into genomic DNA with relatively high frequency during normal replication making DNA more susceptible to strand breakage and mutations. Here we demonstrate that human cells depleted of RNase H2 show impaired cell cycle progression associated with chronic activation of post-replication repair (PRR) and genome instability. We identify a similar phenotype in cells derived from AGS patients, which indeed accumulate rNMPs in genomic DNA and exhibit markers of constitutive PRR and checkpoint activation. Our data indicate that in human cells RNase H2 plays a crucial role in correcting rNMPs misincorporation, preventing DNA damage. Such protective function is compromised in AGS patients and may be linked to unscheduled immune responses. These findings may be relevant to shed further light on the mechanisms involved in AGS pathogenesis.
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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.