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Comparison of K-Ras and N-Ras Mutagenic Hot Spots for UVC Damage

[Image: see text] It has been well established that mutations in K-Ras and N-Ras proto-oncogenes can convert them into active oncogenes. Current molecular cancer research has been focused on determining the key steps by which cellular genes become oncogenes and not on the underlying and fundamental...

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Autores principales: Nair, Sindhu G., Loppnow, Glen R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410678/
https://www.ncbi.nlm.nih.gov/pubmed/30873508
http://dx.doi.org/10.1021/acsomega.8b03017
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author Nair, Sindhu G.
Loppnow, Glen R.
author_facet Nair, Sindhu G.
Loppnow, Glen R.
author_sort Nair, Sindhu G.
collection PubMed
description [Image: see text] It has been well established that mutations in K-Ras and N-Ras proto-oncogenes can convert them into active oncogenes. Current molecular cancer research has been focused on determining the key steps by which cellular genes become oncogenes and not on the underlying and fundamental chemical damage mechanism and susceptibility to damage. In this study, we investigate the damage hot spots present in the N-Ras and K-Ras genes upon exposure to UVC radiation. Detection of damage is accomplished by a simple, sensitive, mix-and-read assay using an EvaGreen probe in a 96-well microtiter plate. Our results show that, although there is high degree of sequential similarities among K-Ras and N-Ras genes, they show different degrees of UV damage in different portions of their genomes. Our experiments demonstrate that overall, the K-Ras genome is more prone to UVC damage than the N-Ras genome. We observe that the extent of damage increases with increasing number of TTs in a sequence, consistent with previous results that show that thymine cyclobutyl photodimers are the primary DNA damage photoproducts upon UVC irradiation. This understanding of the effect of UVC radiation on various codons of K-Ras and N-Ras genes will help to increase our understanding about hot spots of DNA damage and the chemical damage mechanism.
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spelling pubmed-64106782019-03-12 Comparison of K-Ras and N-Ras Mutagenic Hot Spots for UVC Damage Nair, Sindhu G. Loppnow, Glen R. ACS Omega [Image: see text] It has been well established that mutations in K-Ras and N-Ras proto-oncogenes can convert them into active oncogenes. Current molecular cancer research has been focused on determining the key steps by which cellular genes become oncogenes and not on the underlying and fundamental chemical damage mechanism and susceptibility to damage. In this study, we investigate the damage hot spots present in the N-Ras and K-Ras genes upon exposure to UVC radiation. Detection of damage is accomplished by a simple, sensitive, mix-and-read assay using an EvaGreen probe in a 96-well microtiter plate. Our results show that, although there is high degree of sequential similarities among K-Ras and N-Ras genes, they show different degrees of UV damage in different portions of their genomes. Our experiments demonstrate that overall, the K-Ras genome is more prone to UVC damage than the N-Ras genome. We observe that the extent of damage increases with increasing number of TTs in a sequence, consistent with previous results that show that thymine cyclobutyl photodimers are the primary DNA damage photoproducts upon UVC irradiation. This understanding of the effect of UVC radiation on various codons of K-Ras and N-Ras genes will help to increase our understanding about hot spots of DNA damage and the chemical damage mechanism. American Chemical Society 2019-02-15 /pmc/articles/PMC6410678/ /pubmed/30873508 http://dx.doi.org/10.1021/acsomega.8b03017 Text en Copyright © 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Nair, Sindhu G.
Loppnow, Glen R.
Comparison of K-Ras and N-Ras Mutagenic Hot Spots for UVC Damage
title Comparison of K-Ras and N-Ras Mutagenic Hot Spots for UVC Damage
title_full Comparison of K-Ras and N-Ras Mutagenic Hot Spots for UVC Damage
title_fullStr Comparison of K-Ras and N-Ras Mutagenic Hot Spots for UVC Damage
title_full_unstemmed Comparison of K-Ras and N-Ras Mutagenic Hot Spots for UVC Damage
title_short Comparison of K-Ras and N-Ras Mutagenic Hot Spots for UVC Damage
title_sort comparison of k-ras and n-ras mutagenic hot spots for uvc damage
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410678/
https://www.ncbi.nlm.nih.gov/pubmed/30873508
http://dx.doi.org/10.1021/acsomega.8b03017
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