ArticleNucleic acids research2018
The deoxyribose phosphate lyase of DNA polymerase β suppresses a processive DNA synthesis to prevent trinucleotide repeat instability.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 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
6 citing papers in PubMed, 8 citations in OpenAlex.
- Interlocking activities of DNA polymerase β in the base excision repair pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Polymorphic mutations in the polb gene promoter and their impact on transcriptional activity.Thoracic cancer · 2022Article
- When DNA Polymerases Multitask: Functions Beyond Nucleotidyl Transfer.Frontiers in molecular biosciences · 2021Review
- Trinucleotide repeat instability via DNA base excision repair.DNA repair · 2020Review
- Quaternary structural diversity in eukaryotic DNA polymerases: monomeric to multimeric form.Current genetics · 2020Review
- On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability.The Journal of biological chemistry · 2020Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Trinucleotide repeat (TNR) instability is associated with over 42 neurodegenerative diseases and cancer, for which the molecular mechanisms remain to be elucidated. We have shown that the DNA base excision repair (BER) pathway and its central component, DNA polymerase β (pol β), in particular, its polymerase activity plays an active role in regulating somatic TNR instability. Herein, we revealed a unique role of the pol β dRP lyase in preventing somatic TNR instability. We found that deficiency of pol β deoxyribose phosphate (dRP) lyase activity locked the pol β dRP lyase domain to a dRP group, and this 'tethered' pol β to its template forcing the polymerase to perform a processive DNA synthesis. This subsequently promoted DNA strand slippage allowing pol β to skip over a template loop and causing TNR deletion. We showed that the effects were eliminated by complementation of the dRP lyase deficiency with wild-type pol β protein. The results indicate that pol β dRP lyase activity restrained the pol β-dRP interaction to suppress a pol β processive DNA synthesis, thereby preventing TNR deletion. This further implicates a potential of pol β dRP lyase inhibition as a novel treatment of TNR-expansion diseases.
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Registered trials
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