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Structural, energetic and dynamic properties of guanine(C8)–thymine(N3) cross-links in DNA provide insights on susceptibility to nucleotide excision repair
The one-electron oxidation of guanine in DNA by carbonate radical anions, a decomposition product of peroxynitrosocarbonate which is associated with the inflammatory response, can lead to the formation of intrastrand cross-links between guanine and thymine bases [Crean et al. (Oxidation of single-st...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Oxford University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315297/ https://www.ncbi.nlm.nih.gov/pubmed/22135299 http://dx.doi.org/10.1093/nar/gkr1087 |
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author | Ding, Shuang Kropachev, Konstantin Cai, Yuqin Kolbanovskiy, Marina Durandina, Svetlana A. Liu, Zhi Shafirovich, Vladimir Broyde, Suse Geacintov, Nicholas E. |
author_facet | Ding, Shuang Kropachev, Konstantin Cai, Yuqin Kolbanovskiy, Marina Durandina, Svetlana A. Liu, Zhi Shafirovich, Vladimir Broyde, Suse Geacintov, Nicholas E. |
author_sort | Ding, Shuang |
collection | PubMed |
description | The one-electron oxidation of guanine in DNA by carbonate radical anions, a decomposition product of peroxynitrosocarbonate which is associated with the inflammatory response, can lead to the formation of intrastrand cross-links between guanine and thymine bases [Crean et al. (Oxidation of single-stranded oligonucleotides by carbonate radical anions: generating intrastrand cross-links between guanine and thymine bases separated by cytosines. Nucleic Acids Res. 2008; 36: 742–755.)]. These involve covalent bonds between the C8 positions of guanine (G*) and N3 of thymine (T*) in 5′-d(…G*pT*…) and 5′-d(…G*pCpT*…) sequence contexts. We have performed nucleotide excision repair (NER) experiments in human HeLa cell extracts which show that the G*CT* intrastrand cross-link is excised with approximately four times greater efficiency than the G*T* cross-link embedded in 135-mer DNA duplexes. In addition, thermal melting studies reveal that both lesions significantly destabilize duplex DNA, and that the destabilization induced by the G*CT* cross-link is considerably greater. Consistent with this difference in NER, our computations show that both lesions dynamically distort and destabilize duplex DNA. They disturb Watson–Crick base-pairing and base-stacking interactions, and cause untwisting and minor groove opening. These structural perturbations are much more pronounced in the G*CT* than in the G*T* cross-link. Our combined experimental and computational studies provide structural and thermodynamic understanding of the features of the damaged duplexes that produce the most robust NER response. |
format | Online Article Text |
id | pubmed-3315297 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-33152972012-03-30 Structural, energetic and dynamic properties of guanine(C8)–thymine(N3) cross-links in DNA provide insights on susceptibility to nucleotide excision repair Ding, Shuang Kropachev, Konstantin Cai, Yuqin Kolbanovskiy, Marina Durandina, Svetlana A. Liu, Zhi Shafirovich, Vladimir Broyde, Suse Geacintov, Nicholas E. Nucleic Acids Res Genome Integrity, Repair and Replication The one-electron oxidation of guanine in DNA by carbonate radical anions, a decomposition product of peroxynitrosocarbonate which is associated with the inflammatory response, can lead to the formation of intrastrand cross-links between guanine and thymine bases [Crean et al. (Oxidation of single-stranded oligonucleotides by carbonate radical anions: generating intrastrand cross-links between guanine and thymine bases separated by cytosines. Nucleic Acids Res. 2008; 36: 742–755.)]. These involve covalent bonds between the C8 positions of guanine (G*) and N3 of thymine (T*) in 5′-d(…G*pT*…) and 5′-d(…G*pCpT*…) sequence contexts. We have performed nucleotide excision repair (NER) experiments in human HeLa cell extracts which show that the G*CT* intrastrand cross-link is excised with approximately four times greater efficiency than the G*T* cross-link embedded in 135-mer DNA duplexes. In addition, thermal melting studies reveal that both lesions significantly destabilize duplex DNA, and that the destabilization induced by the G*CT* cross-link is considerably greater. Consistent with this difference in NER, our computations show that both lesions dynamically distort and destabilize duplex DNA. They disturb Watson–Crick base-pairing and base-stacking interactions, and cause untwisting and minor groove opening. These structural perturbations are much more pronounced in the G*CT* than in the G*T* cross-link. Our combined experimental and computational studies provide structural and thermodynamic understanding of the features of the damaged duplexes that produce the most robust NER response. Oxford University Press 2012-03 2011-11-30 /pmc/articles/PMC3315297/ /pubmed/22135299 http://dx.doi.org/10.1093/nar/gkr1087 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Genome Integrity, Repair and Replication Ding, Shuang Kropachev, Konstantin Cai, Yuqin Kolbanovskiy, Marina Durandina, Svetlana A. Liu, Zhi Shafirovich, Vladimir Broyde, Suse Geacintov, Nicholas E. Structural, energetic and dynamic properties of guanine(C8)–thymine(N3) cross-links in DNA provide insights on susceptibility to nucleotide excision repair |
title | Structural, energetic and dynamic properties of guanine(C8)–thymine(N3) cross-links in DNA provide insights on susceptibility to nucleotide excision repair |
title_full | Structural, energetic and dynamic properties of guanine(C8)–thymine(N3) cross-links in DNA provide insights on susceptibility to nucleotide excision repair |
title_fullStr | Structural, energetic and dynamic properties of guanine(C8)–thymine(N3) cross-links in DNA provide insights on susceptibility to nucleotide excision repair |
title_full_unstemmed | Structural, energetic and dynamic properties of guanine(C8)–thymine(N3) cross-links in DNA provide insights on susceptibility to nucleotide excision repair |
title_short | Structural, energetic and dynamic properties of guanine(C8)–thymine(N3) cross-links in DNA provide insights on susceptibility to nucleotide excision repair |
title_sort | structural, energetic and dynamic properties of guanine(c8)–thymine(n3) cross-links in dna provide insights on susceptibility to nucleotide excision repair |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315297/ https://www.ncbi.nlm.nih.gov/pubmed/22135299 http://dx.doi.org/10.1093/nar/gkr1087 |
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