ArticleProceedings of the National Academy of Sciences of the United States of America2011
Topoisomerase 1 provokes the formation of short deletions in repeated sequences upon high transcription in Saccharomyces cerevisiae.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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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.
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Who cites it
63 citing papers in PubMed, 75 citations in OpenAlex.
- Article
- Ribonucleotide errors, RNase HII, and ribonucleotide excision repair.Critical reviews in biochemistry and molecular biology · 2026Review
- R-loop disruption triggers irreversible topoisomerase 1-DNA cleavage complex formation during AID-dependent IgH gene diversification.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Sex differences in transcription-associated mutagenesis in the human germline.bioRxiv : the preprint server for biology · 2025Article
- The low endoribonuclease activity and lack of rNMP preference of human mitochondrial topoisomerase 1 protect against ribonucleotide-dependent deletions.Nucleic acids research · 2025Article
- Genome Instability Induced by Topoisomerase Misfunction.International journal of molecular sciences · 2024Review
- Deletions initiated by the vaccinia virus TopIB protein in yeast.DNA repair · 2024Article
- Transcription as source of genetic heterogeneity in budding yeast.Yeast (Chichester, England) · 2024Review
- Review
- Spontaneous deamination of cytosine to uracil is biased to the non-transcribed DNA strand in yeast.DNA repair · 2023Article
- Ago2 and a miRNA reduce Topoisomerase 1 for enhancing DNA cleavage in antibody diversification by activation-induced cytidine deaminase.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Article
- RNases H1 and H2: guardians of the stability of the nuclear genome when supply of dNTPs is limiting for DNA synthesis.Current genetics · 2020Review
- Homologous recombination and Mus81 promote replication completion in response to replication fork blockage.EMBO reports · 2020Article
- Molecular and physiological consequences of faulty eukaryotic ribonucleotide excision repair.The EMBO journal · 2020Review
- 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
- Review
- 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
3 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High transcription is associated with genetic instability, notably increased spontaneous mutation rates, which is a phenomenon termed Transcription-Associated-Mutagenesis (TAM). In this study, we investigated TAM using the chromosomal CAN1 gene under the transcriptional control of two strong and inducible promoters (pGAL1 and pTET) in Saccharomyces cerevisiae. Both pTET- and pGAL1-driven high transcription at the CAN1 gene result in enhanced spontaneous mutation rates. Comparison of both promoters reveals differences in the type of mutagenesis, except for short (-2 and -3 nt) deletions, which depend only on the level of transcription. This mutation type, characteristic of TAM, is sequence dependent, occurring prefentially at di- and trinucleotides repeats, notably at two mutational hotspots encompassing the same 5'-ACATAT-3' sequence. To explore the mechanisms underlying the formation of short deletions in the course of TAM, we have determined Can(R) mutation spectra in yeast mutants affected in DNA metabolism. We identified topoisomerase 1-deficient strains (top1Δ) that specifically abolish the formation of short deletions under high transcription. The rate of the formation of (-2/-3nt) deletions is also reduced in the absence of RAD1 and MUS81 genes, involved in the repair of Top1p-DNA covalent complex. Furthermore ChIP analysis reveals an enrichment of trapped Top1p in the CAN1 ORF under high transcription. We propose a model, in which the repair of trapped Top1p-DNA complexes provokes the formation of short deletion in S. cerevisiae. This study reveals unavoidable conflicts between Top1p and the transcriptional machinery and their potential impact on genome stability.
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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.