ArticleMolecular and cellular biology2010
Convergent transcription through a long CAG tract destabilizes repeats and induces apoptosis.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 59 citations in OpenAlex.
- All three MutL complexes are required for repeat expansion in a human stem cell model of CAG-repeat expansion mediated glutaminase deficiency.Scientific reports · 2024Article
- All three MutL complexes are required for repeat expansion in a human stem cell model of CAG-repeat expansion mediated glutaminase deficiency.bioRxiv : the preprint server for biology · 2024Article
- Splice modulators target PMS1 to reduce somatic expansion of the Huntington's disease-associated CAG repeat.Nature communications · 2024Article
- Flap Endonuclease 1 Endonucleolytically Processes RNA to Resolve R-Loops through DNA Base Excision Repair.Genes · 2022Article
- The RNA export and RNA decay complexes THO and TRAMP prevent transcription-replication conflicts, DNA breaks, and CAG repeat contractions.PLoS biology · 2022Article
- CAG RNAs induce DNA damage and apoptosis by silencingProceedings of the National Academy of Sciences of the United States of America · 2021Article
- On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability.The Journal of biological chemistry · 2020Review
- The role of fork stalling and DNA structures in causing chromosome fragility.Genes, chromosomes & cancer · 2019Review
- R-loop generation during transcription: Formation, processing and cellular outcomes.DNA repair · 2018Review
- R Loops and Links to Human Disease.Journal of molecular biology · 2017Review
- Antisense transcription of the myotonic dystrophy locus yields low-abundant RNAs with and without (CAG)n repeat.RNA biology · 2017Article
- RNA biology of disease-associated microsatellite repeat expansions.Acta neuropathologica communications · 2017Review
- Close encounters: Moving along bumps, breaks, and bubbles on expanded trinucleotide tracts.DNA repair · 2017Review
- RNA toxicity and foci formation in microsatellite expansion diseases.Current opinion in genetics & development · 2017Review
- Selection pressure on human STR loci and its relevance in repeat expansion disease.Molecular genetics and genomics : MGG · 2016Article
- Mismatch repair enhances convergent transcription-induced cell death at trinucleotide repeats by activating ATR.DNA repair · 2016Article
- Cancer therapies activate RIG-I-like receptor pathway through endogenous non-coding RNAs.Oncotarget · 2016Article
- Fanconi anemia pathway regulates convergent transcription-induced cell death at trinucleotide repeats in human cells.Postdoc journal : a journal of postdoctoral research and postdoctoral affairs · 2016Article
- Regulation of recombination at yeast nuclear pores controls repair and triplet repeat stability.Genes & development · 2015Article
- Twisting right to left: A…A mismatch in a CAG trinucleotide repeat overexpansion provokes left-handed Z-DNA conformation.PLoS computational biology · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Short repetitive sequences are common in the human genome, and many fall within transcription units. We have previously shown that transcription through CAG repeat tracts destabilizes them in a way that depends on transcription-coupled nucleotide excision repair and mismatch repair. Recent observations that antisense transcription accompanies sense transcription in many human genes led us to test the effects of antisense transcription on triplet repeat instability in human cells. Here, we report that simultaneous sense and antisense transcription (convergent transcription) initiated from two inducible promoters flanking a CAG95 tract in a nonessential gene enhances repeat instability synergistically, arrests the cell cycle, and causes massive cell death via apoptosis. Using chemical inhibitors and small interfering RNA (siRNA) knockdowns, we identified the ATR (ataxia-telangiectasia mutated [ATM] and Rad3 related) signaling pathway as a key mediator of this cellular response. RNA polymerase II, replication protein A (RPA), and components of the ATR signaling pathway accumulate at convergently transcribed repeat tracts, accompanied by phosphorylation of ATR, CHK1, and p53. Cell death depends on simultaneous sense and antisense transcription and is proportional to their relative levels, it requires the presence of the repeat tract, and it occurs in both proliferating and nonproliferating cells. Convergent transcription through a CAG repeat represents a novel mechanism for triggering a cellular stress response, one that is initiated by events at a single locus in the genome and resembles the response to DNA damage.
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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.