دورية أكاديمية
أعرض في EDS

Quantification of Intracellular DNA-Protein Cross-Links with N7-Methyl-2'-Deoxyguanosine and Their Contribution to Cytotoxicity.

التفاصيل البيبلوغرافية
العنوان: Quantification of Intracellular DNA-Protein Cross-Links with N7-Methyl-2'-Deoxyguanosine and Their Contribution to Cytotoxicity.
المؤلفون: Wen T; Department of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, Maryland 21218, United States., Zhao S; Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, 81377 Munich, Germany., Stingele J; Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, 81377 Munich, Germany., Ravanat JL; Univ. Grenoble Alpes, CEA, CNRS, Grenoble INP, IRIG, SyMMES, 38000 Grenoble, France., Greenberg MM; Department of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, Maryland 21218, United States.
المصدر: Chemical research in toxicology [Chem Res Toxicol] 2024 May 20; Vol. 37 (5), pp. 814-823. Date of Electronic Publication: 2024 Apr 23.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 8807448 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5010 (Electronic) Linking ISSN: 0893228X NLM ISO Abbreviation: Chem Res Toxicol Subsets: MEDLINE
أسماء مطبوعة: Publication: Washington Dc : American Chemical Society
Original Publication: Washington, DC : American Chemical Society, c1988-
مواضيع طبية MeSH: DNA*/metabolism , DNA*/chemistry , DNA*/drug effects , Deoxyguanosine*/analogs & derivatives , Deoxyguanosine*/metabolism , Deoxyguanosine*/chemistry , Methyl Methanesulfonate*/chemistry , Methyl Methanesulfonate*/pharmacology, Humans ; HeLa Cells ; Tandem Mass Spectrometry ; Cell Survival/drug effects ; DNA Damage/drug effects ; Cross-Linking Reagents/chemistry ; DNA-Binding Proteins
مستخلص: The major product of DNA-methylating agents, N7-methyl-2'-deoxyguanosine (MdG), is a persistent lesion in vivo , but it is not believed to have a large direct physiological impact. However, MdG reacts with histone proteins to form reversible DNA-protein cross-links (DPC MdG ), a family of DNA lesions that can significantly threaten cell survival. In this paper, we developed a tandem mass spectrometry method for quantifying the amounts of MdG and DPC MdG in nuclear DNA by taking advantage of their chemical lability and the concurrent release of N7-methylguanine. Using this method, we determined that DPC MdG is formed in less than 1% yield based upon the levels of MdG in methyl methanesulfonate (MMS)-treated HeLa cells. Despite its low chemical yield, DPC MdG contributes to MMS cytotoxicity. Consequently, cells that lack efficient DPC repair by the DPC protease SPRTN are hypersensitive to MMS. This investigation shows that the downstream chemical and biochemical effects of initially formed DNA damage can have significant biological consequences. With respect to MdG formation, the initial DNA lesion is only the beginning.
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معلومات مُعتمدة: R35 GM131736 United States GM NIGMS NIH HHS
المشرفين على المادة: 0 (SPRTN protein, human)
تواريخ الأحداث: Date Created: 20240423 Date Completed: 20240520 Latest Revision: 20240522
رمز التحديث: 20240522
مُعرف محوري في PubMed: PMC11105979
DOI: 10.1021/acs.chemrestox.4c00076
PMID: 38652696
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-5010
DOI:10.1021/acs.chemrestox.4c00076