ArticleNucleic acids research2016
Parallel analysis of ribonucleotide-dependent deletions produced by yeast Top1 in vitro and in vivo.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Deletions initiated by the vaccinia virus TopIB protein in yeast.DNA repair · 2024Article
- The Ultimate (Mis)match: When DNA Meets RNA.Cells · 2021Review
- Trapped topoisomerase II initiates formation of de novo duplications via the nonhomologous end-joining pathway in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- High density of unrepaired genomic ribonucleotides leads to Topoisomerase 1-mediated severe growth defects in absence of ribonucleotide reductase.Nucleic acids research · 2020Article
- One, No One, and One Hundred Thousand: The Many Forms of Ribonucleotides in DNA.International journal of molecular sciences · 2020Review
- Genome-wide mutagenesis resulting from topoisomerase 1-processing of unrepaired ribonucleotides in DNA.DNA repair · 2019Article
- Deletions associated with stabilization of the Top1 cleavage complex in yeast are products of the nonhomologous end-joining pathway.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Effects of camptothecin or TOP1 overexpression on genetic stability in Saccharomyces cerevisiae.DNA repair · 2017Article
- Ribonucleotides and Transcription-Associated Mutagenesis in Yeast.Journal of molecular biology · 2017Review
- The Top1 paradox: Friend and foe of the eukaryotic genome.DNA repair · 2017Review
- Topoisomerase I-mediated cleavage at unrepaired ribonucleotides generates DNA double-strand breaks.The EMBO journal · 2017Article
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Authors and funding
6 authors at 6 institutions in 1 country.
Funding
Abstract
Ribonucleotides are the most abundant non-canonical component of yeast genomic DNA and their persistence is associated with a distinctive mutation signature characterized by deletion of a single repeat unit from a short tandem repeat. These deletion events are dependent on DNA topoisomerase I (Top1) and are initiated by Top1 incision at the relevant ribonucleotide 3'-phosphodiester. A requirement for the re-ligation activity of Top1 led us to propose a sequential cleavage model for Top1-dependent mutagenesis at ribonucleotides. Here, we test key features of this model via parallel in vitro and in vivo analyses. We find that the distance between two Top1 cleavage sites determines the deletion size and that this distance is inversely related to the deletion frequency. Following the creation of a gap by two Top1 cleavage events, the tandem repeat provides complementarity that promotes realignment to a nick and subsequent Top1-mediated ligation. Complementarity downstream of the gap promotes deletion formation more effectively than does complementarity upstream of the gap, consistent with constraints to realignment of the strand to which Top1 is covalently bound. Our data fortify sequential Top1 cleavage as the mechanism for ribonucleotide-dependent deletions and provide new insight into the component steps of this process.
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