Interstrand cross-links arising from strand breaks at true abasic sites in duplex DNA
| العنوان: | Interstrand cross-links arising from strand breaks at true abasic sites in duplex DNA |
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| المؤلفون: | Nathan E. Price, Kevin M. Johnson, Yinsheng Wang, Zhiyu Yang, Kent S. Gates |
| المصدر: | Nucleic Acids Research |
| بيانات النشر: | Oxford University Press (OUP), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | DNA Replication, 0301 basic medicine, Apurinic Acid, DNA polymerase, 010402 general chemistry, Cleavage (embryo), 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Chemical Biology and Nucleic Acid Chemistry, Genetics, DNA Cleavage, Polymerase, biology, DNA replication, DNA, 0104 chemical sciences, genomic DNA, 030104 developmental biology, chemistry, Duplex (building), biology.protein, Biophysics, Nucleic Acid Conformation, Cytokinesis, DNA Damage |
| الوصف: | Interstrand cross-links are exceptionally bioactive DNA lesions. Endogenous generation of interstrand cross-links in genomic DNA may contribute to aging, neurodegeneration, and cancer. Abasic (Ap) sites are common lesions in genomic DNA that readily undergo spontaneous and amine-catalyzed strand cleavage reactions that generate a 2,3-didehydro-2,3-dideoxyribose sugar remnant (3’ddR5p) at the 3’-terminus of the strand break. Interestingly, this strand scission process leaves an electrophilic α,β-unsaturated aldehyde residue embedded within the resulting nicked duplex. Here we present evidence that 3’ddR5p derivatives generated by spermine-catalyzed strand cleavage at Ap sites in duplex DNA can react with adenine residues on the opposing strand to generate a complex lesion consisting of an interstrand cross-link adjacent to a strand break. The cross-link blocks DNA replication by ϕ29 DNA polymerase, a highly processive polymerase enzyme that couples synthesis with strand displacement. This suggests that 3’ddR5p-derived cross-links have the potential to block critical cellular DNA transactions that require strand separation. LC-MS/MS methods developed herein provide powerful tools for studying the occurrence and properties of these cross-links in biochemical and biological systems. |
| تدمد: | 1362-4962 0305-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::179fec8549d1b1463e3791073487135a https://doi.org/10.1093/nar/gkx394 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....179fec8549d1b1463e3791073487135a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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