دورية أكاديمية
أعرض في EDS

Promoter dependent RNA polymerase II bypass of the epimerizable DNA lesion, Fapy•dG and 8-Oxo-2'-deoxyguanosine.

التفاصيل البيبلوغرافية
العنوان: Promoter dependent RNA polymerase II bypass of the epimerizable DNA lesion, Fapy•dG and 8-Oxo-2'-deoxyguanosine.
المؤلفون: Gao S; Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA., Tahara Y; Department of Chemistry, Stanford University, Stanford, CA 94305, USA., Kool ET; Department of Chemistry, Stanford University, Stanford, CA 94305, USA., Greenberg MM; Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA.
المصدر: Nucleic acids research [Nucleic Acids Res] 2024 Jul 22; Vol. 52 (13), pp. 7437-7446.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
مواضيع طبية MeSH: RNA Polymerase II*/metabolism , RNA Polymerase II*/genetics , 8-Hydroxy-2'-Deoxyguanosine*/metabolism , Promoter Regions, Genetic* , Deoxyguanosine*/analogs & derivatives , Deoxyguanosine*/metabolism , DNA Damage*, Humans ; HEK293 Cells ; HeLa Cells ; DNA Repair ; Transcription, Genetic ; Pyrimidines ; Pyrimidine Dimers/metabolism ; Pyrimidine Dimers/genetics
مستخلص: Formamidopyrimidine (Fapy•dG) is a major lesion arising from oxidation of dG that is produced from a common chemical precursor of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo). In human cells, replication of single-stranded shuttle vectors containing Fapy•dG is more mutagenic than 8-OxodGuo. Here, we present the first data regarding promoter dependent RNA polymerase II bypass of Fapy•dG. 8-OxodGuo bypass was examined side-by-side. Experiments were carried out using double-stranded shuttle vectors in HeLa cell nuclear lysates and in HEK 293T cells. The lesions do not significantly block transcriptional bypass efficiency. Less than 2% adenosine incorporation occurred in cells when the lesions were base paired with dC. Inhibiting base excision repair in HEK 293T cells significantly increased adenosine incorporation, particularly from Fapy•dG:dC bypass which yielded ∼25% adenosine incorporation. No effect was detected upon transcriptional bypass of either lesion in nucleotide excision repair deficient cells. Transcriptional mutagenesis was significantly higher when shuttle vectors containing dA opposite one of the lesions were employed. For Fapy•dG:dA bypass, adenosine incorporation was greater than 85%; whereas 8-OxodGuo:dA yielded >20% point mutations. The combination of more frequent replication mistakes and greater error-prone Pol II bypass suggest that Fapy•dG is more mutagenic than 8-OxodGuo.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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معلومات مُعتمدة: R01 CA217809 United States CA NCI NIH HHS; R01 ES027558 United States ES NIEHS NIH HHS; R35 GM131736 United States GM NIGMS NIH HHS; GM-131736 United States NH NIH HHS
المشرفين على المادة: EC 2.7.7.- (RNA Polymerase II)
88847-89-6 (8-Hydroxy-2'-Deoxyguanosine)
G9481N71RO (Deoxyguanosine)
0 (Pyrimidines)
0 (Pyrimidine Dimers)
133310-38-0 (2,6-diamino-4-hydroxy-5-formamidopyrimidine)
تواريخ الأحداث: Date Created: 20240622 Date Completed: 20240721 Latest Revision: 20240820
رمز التحديث: 20240820
مُعرف محوري في PubMed: PMC11260475
DOI: 10.1093/nar/gkae529
PMID: 38908029
قاعدة البيانات: MEDLINE
الوصف
تدمد:1362-4962
DOI:10.1093/nar/gkae529