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Dynamic accumulation of cyclobutane pyrimidine dimers and its response to changes in DNA conformation

Photochemical dimerization of adjacent pyrimidines is fundamental to the creation of mutagenic hotspots caused by ultraviolet light. Distribution of the resulting lesions (cyclobutane pyrimidine dimers, CPDs) is already known to be highly variable in cells, and in vitro models have implicated DNA co...

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Autores principales: Moirangthem, Ravina, Gamage, Manusha N, Rokita, Steven E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10287945/
https://www.ncbi.nlm.nih.gov/pubmed/37207339
http://dx.doi.org/10.1093/nar/gkad434
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author Moirangthem, Ravina
Gamage, Manusha N
Rokita, Steven E
author_facet Moirangthem, Ravina
Gamage, Manusha N
Rokita, Steven E
author_sort Moirangthem, Ravina
collection PubMed
description Photochemical dimerization of adjacent pyrimidines is fundamental to the creation of mutagenic hotspots caused by ultraviolet light. Distribution of the resulting lesions (cyclobutane pyrimidine dimers, CPDs) is already known to be highly variable in cells, and in vitro models have implicated DNA conformation as a major basis for this observation. Past efforts have primarily focused on mechanisms that influence CPD formation and have rarely considered contributions of CPD reversion. However, reversion is competitive under the standard conditions of 254 nm irradiation as illustrated in this report based on the dynamic response of CPDs to changes in DNA conformation. A periodic profile of CPDs was recreated in DNA held in a bent conformation by λ repressor. After linearization of this DNA, the CPD profile relaxed to its characteristic uniform distribution over a similar time of irradiation to that required to generate the initial profile. Similarly, when a T tract was released from a bent conformation, its CPD profile converted under further irradiation to that consistent with a linear T tract. This interconversion of CPDs indicates that both its formation and reversion exert control on CPD populations long before photo-steady-state conditions are achieved and suggests that the dominant sites of CPDs will evolve as DNA conformation changes in response to natural cellular processes.
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spelling pubmed-102879452023-06-24 Dynamic accumulation of cyclobutane pyrimidine dimers and its response to changes in DNA conformation Moirangthem, Ravina Gamage, Manusha N Rokita, Steven E Nucleic Acids Res Chemical Biology and Nucleic Acid Chemistry Photochemical dimerization of adjacent pyrimidines is fundamental to the creation of mutagenic hotspots caused by ultraviolet light. Distribution of the resulting lesions (cyclobutane pyrimidine dimers, CPDs) is already known to be highly variable in cells, and in vitro models have implicated DNA conformation as a major basis for this observation. Past efforts have primarily focused on mechanisms that influence CPD formation and have rarely considered contributions of CPD reversion. However, reversion is competitive under the standard conditions of 254 nm irradiation as illustrated in this report based on the dynamic response of CPDs to changes in DNA conformation. A periodic profile of CPDs was recreated in DNA held in a bent conformation by λ repressor. After linearization of this DNA, the CPD profile relaxed to its characteristic uniform distribution over a similar time of irradiation to that required to generate the initial profile. Similarly, when a T tract was released from a bent conformation, its CPD profile converted under further irradiation to that consistent with a linear T tract. This interconversion of CPDs indicates that both its formation and reversion exert control on CPD populations long before photo-steady-state conditions are achieved and suggests that the dominant sites of CPDs will evolve as DNA conformation changes in response to natural cellular processes. Oxford University Press 2023-05-19 /pmc/articles/PMC10287945/ /pubmed/37207339 http://dx.doi.org/10.1093/nar/gkad434 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Chemical Biology and Nucleic Acid Chemistry
Moirangthem, Ravina
Gamage, Manusha N
Rokita, Steven E
Dynamic accumulation of cyclobutane pyrimidine dimers and its response to changes in DNA conformation
title Dynamic accumulation of cyclobutane pyrimidine dimers and its response to changes in DNA conformation
title_full Dynamic accumulation of cyclobutane pyrimidine dimers and its response to changes in DNA conformation
title_fullStr Dynamic accumulation of cyclobutane pyrimidine dimers and its response to changes in DNA conformation
title_full_unstemmed Dynamic accumulation of cyclobutane pyrimidine dimers and its response to changes in DNA conformation
title_short Dynamic accumulation of cyclobutane pyrimidine dimers and its response to changes in DNA conformation
title_sort dynamic accumulation of cyclobutane pyrimidine dimers and its response to changes in dna conformation
topic Chemical Biology and Nucleic Acid Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10287945/
https://www.ncbi.nlm.nih.gov/pubmed/37207339
http://dx.doi.org/10.1093/nar/gkad434
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