ArticleProceedings of the National Academy of Sciences of the United States of America2014
Repair of DNA double-strand breaks by templated nucleotide sequence insertions derived from distant regions of the genome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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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.
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Who cites it
48 citing papers in PubMed, 78 citations in OpenAlex.
- The interplay of DNA damage, epigenetics and tumour heterogeneity in driving cancer cell fitness.Nature communications · 2025Review
- RNA transcripts serve as a template for double-strand break repair in human cells.Nature communications · 2025Article
- RPA and Rad27 limit templated and inverted insertions at DNA breaks.Nucleic acids research · 2025Article
- Decoding the complexity of on-target integration: characterizing DNA insertions at the CRISPR-Cas9 targeted locus using nanopore sequencing.BMC genomics · 2024Article
- Human Endogenous Retrovirus-K (HML-2)-Related Genetic Variation: Human Genome Diversity and Disease.Genes · 2023Review
- Mechanisms of insertions at a DNA double-strand break.Molecular cell · 2023Article
- The fine-scale recombination rate variation and associations with genomic features in a butterfly.Genome research · 2023Article
- The Molecular Mechanisms and Therapeutic Prospects of Alternative Lengthening of Telomeres (ALT).Cancers · 2023Review
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- Different classes of genomic inserts contribute to human antibody diversity.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The potential and limitation of targeted chromosomal breakpoint sequencing for theAmerican journal of cancer research · 2022Article
- Review
- Article
- Telomeric-Like Repeats Flanked by Sequences Retrotranscribed from the Telomerase RNA Inserted at DNA Double-Strand Break Sites during Vertebrate Genome Evolution.International journal of molecular sciences · 2021Article
- Phf5a regulates DNA repair in class switch recombination via p400 and histone H2A variant deposition.The EMBO journal · 2021Article
- The Ultimate (Mis)match: When DNA Meets RNA.Cells · 2021Review
- SAMHD1 restrains aberrant nucleotide insertions at repair junctions generated by DNA end joining.Nucleic acids research · 2021Article
- Article
- RNA: a double-edged sword in genome maintenance.Nature reviews. Genetics · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
We used the I-SceI endonuclease to produce DNA double-strand breaks (DSBs) and observed that a fraction of these DSBs were repaired by insertion of sequences, which we termed "templated sequence insertions" (TSIs), derived from distant regions of the genome. These TSIs were derived from genic, retrotransposon, or telomere sequences and were not deleted from the donor site in the genome, leading to the hypothesis that they were derived from reverse-transcribed RNA. Cotransfection of RNA and an I-SceI expression vector demonstrated insertion of RNA-derived sequences at the DNA-DSB site, and TSIs were suppressed by reverse-transcriptase inhibitors. Both observations support the hypothesis that TSIs were derived from RNA templates. In addition, similar insertions were detected at sites of DNA DSBs induced by transcription activator-like effector nuclease proteins. Whole-genome sequencing of myeloma cell lines revealed additional TSIs, demonstrating that repair of DNA DSBs via insertion was not restricted to experimentally produced DNA DSBs. Analysis of publicly available databases revealed that many of these TSIs are polymorphic in the human genome. Taken together, these results indicate that insertional events should be considered as alternatives to gross chromosomal rearrangements in the interpretation of whole-genome sequence data and that this mutagenic form of DNA repair may play a role in genetic disease, exon shuffling, and mammalian evolution.
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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.