ArticleDNA repair2011
Incidence and persistence of 8-oxo-7,8-dihydroguanine within a hairpin intermediate exacerbates a toxic oxidation cycle associated with trinucleotide repeat expansion.
Article in DNA repair, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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
37 citing papers in PubMed, 46 citations in OpenAlex.
- DNA Structure-Dependent Enrichment of Oxidative Lesions.Chemical research in toxicology · 2026Article
- Oxidative damage within alternative DNA structures results in aberrant mutagenic processing.Nucleic acids research · 2025Article
- Recurrent DNA nicks drive massive expansions of (GAA)Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Non-canonical DNA/RNA structures associated with the pathogenesis of Fragile X-associated tremor/ataxia syndrome and Fragile X syndrome.Frontiers in genetics · 2022Review
- Modifiers of CAG/CTG Repeat Instability: Insights from Mammalian Models.Journal of Huntington's disease · 2021Review
- Trinucleotide repeat instability via DNA base excision repair.DNA repair · 2020Review
- MUTYH: Not just polyposis.World journal of clinical oncology · 2020Review
- An oxidized abasic lesion inhibits base excision repair leading to DNA strand breaks in a trinucleotide repeat tract.PloS one · 2018Article
- Differential Ability of Five DNA Glycosylases to Recognize and Repair Damage on Nucleosomal DNA.ACS chemical biology · 2017Article
- Proliferating cell nuclear antigen prevents trinucleotide repeat expansions by promoting repeat deletion and hairpin removal.DNA repair · 2016Article
- Review
- Unique Length-Dependent Biophysical Properties of Repetitive DNA.The journal of physical chemistry. B · 2016Article
- Rate-determining Step of Flap Endonuclease 1 (FEN1) Reflects a Kinetic Bias against Long Flaps and Trinucleotide Repeat Sequences.The Journal of biological chemistry · 2015Article
- AP endonuclease 1 prevents trinucleotide repeat expansion via a novel mechanism during base excision repair.Nucleic acids research · 2015Article
- Impact of alternative DNA structures on DNA damage, DNA repair, and genetic instability.DNA repair · 2014Review
- APE1 incision activity at abasic sites in tandem repeat sequences.Journal of molecular biology · 2014Article
- Base excision repair of tandem modifications in a methylated CpG dinucleotide.The Journal of biological chemistry · 2014Article
- A chemical and kinetic perspective on base excision repair of DNA.Accounts of chemical research · 2014Article
- Base excision repair of oxidative DNA damage coupled with removal of a CAG repeat hairpin attenuates trinucleotide repeat expansion.Nucleic acids research · 2014Article
- Impact of bulge loop size on DNA triplet repeat domains: Implications for DNA repair and expansion.Biopolymers · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The repair protein 8-oxo-7,8-dihydroguanine glycosylase (OGG1) initiates base excision repair (BER) in mammalian cells by removing the oxidized base 8-oxo-7,8-dihydroguanine (8-oxoG) from DNA. Interestingly, OGG1 has been implicated in somatic expansion of the trinucleotide repeat (TNR) sequence CAG/CTG. Furthermore, a 'toxic oxidation cycle' has been proposed for age-dependent expansion in somatic cells. In this cycle, duplex TNR DNA is (1) oxidized by endogenous species; (2) BER is initiated by OGG1 and the DNA is further processed by AP endonuclease 1 (APE1); (3) a stem-loop hairpin forms during strand-displacement synthesis by polymerase β (pol β); (4) the hairpin is ligated and (5) incorporated into duplex DNA to generate an expanded CAG/CTG region. This expanded region is again subject to oxidation and the cycle continues. We reported previously that the hairpin adopted by TNR repeats contains a hot spot for oxidation. This finding prompted us to examine the possibility that the generation of a hairpin during a BER event exacerbates the toxic oxidation cycle due to accumulation of damage. Therefore, in this work we used mixed-sequence and TNR substrates containing a site-specific 8-oxoG lesion to define the kinetic parameters of human OGG1 (hOGG1) activity on duplex and hairpin substrates. We report that hOGG1 activity on TNR duplexes is indistinguishable from a mixed-sequence control. Thus, BER is initiated on TNR sequences as readily as non-repetitive DNA in order to start the toxic oxidation cycle. However, we find that for hairpin substrates hOGG1 has reduced affinity and excises 8-oxoG at a significantly slower rate as compared to duplexes. Therefore, 8-oxoG is expected to accumulate in the hairpin intermediate. This damage-containing hairpin can then be incorporated into duplex, resulting in an expanded TNR tract that now contains an oxidative lesion. Thus, the cycle restarts and the DNA can incrementally expand.
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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.