Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells

UVA-induced mutagenesis was investigated in human pol eta-deficient (XP-V) cells through whole-exome sequencing. In UVA-irradiated cells, the increase in the mutation frequency in deficient cells included a remarkable contribution of C>T transitions, mainly at potential pyrimidine dimer sites. A...

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Autores principales: Moreno, Natália Cestari, de Souza, Tiago Antonio, Garcia, Camila Carrião Machado, Ruiz, Nathalia Quintero, Corradi, Camila, Castro, Ligia Pereira, Munford, Veridiana, Ienne, Susan, Alexandrov, Ludmil B, Menck, Carlos Frederico Martins
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038989/
https://www.ncbi.nlm.nih.gov/pubmed/31853541
http://dx.doi.org/10.1093/nar/gkz1182
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author Moreno, Natália Cestari
de Souza, Tiago Antonio
Garcia, Camila Carrião Machado
Ruiz, Nathalia Quintero
Corradi, Camila
Castro, Ligia Pereira
Munford, Veridiana
Ienne, Susan
Alexandrov, Ludmil B
Menck, Carlos Frederico Martins
author_facet Moreno, Natália Cestari
de Souza, Tiago Antonio
Garcia, Camila Carrião Machado
Ruiz, Nathalia Quintero
Corradi, Camila
Castro, Ligia Pereira
Munford, Veridiana
Ienne, Susan
Alexandrov, Ludmil B
Menck, Carlos Frederico Martins
author_sort Moreno, Natália Cestari
collection PubMed
description UVA-induced mutagenesis was investigated in human pol eta-deficient (XP-V) cells through whole-exome sequencing. In UVA-irradiated cells, the increase in the mutation frequency in deficient cells included a remarkable contribution of C>T transitions, mainly at potential pyrimidine dimer sites. A strong contribution of C>A transversions, potentially due to oxidized bases, was also observed in non-irradiated XP-V cells, indicating that basal mutagenesis caused by oxidative stress may be related to internal tumours in XP-V patients. The low levels of mutations involving T induced by UVA indicate that pol eta is not responsible for correctly replicating T-containing pyrimidine dimers, a phenomenon known as the ‘A-rule’. Moreover, the mutation signature profile of UVA-irradiated XP-V cells is highly similar to the human skin cancer profile, revealing how studies involving cells deficient in DNA damage processing may be useful to understand the mechanisms of environmentally induced carcinogenesis.
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spelling pubmed-70389892020-03-02 Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells Moreno, Natália Cestari de Souza, Tiago Antonio Garcia, Camila Carrião Machado Ruiz, Nathalia Quintero Corradi, Camila Castro, Ligia Pereira Munford, Veridiana Ienne, Susan Alexandrov, Ludmil B Menck, Carlos Frederico Martins Nucleic Acids Res Genome Integrity, Repair and Replication UVA-induced mutagenesis was investigated in human pol eta-deficient (XP-V) cells through whole-exome sequencing. In UVA-irradiated cells, the increase in the mutation frequency in deficient cells included a remarkable contribution of C>T transitions, mainly at potential pyrimidine dimer sites. A strong contribution of C>A transversions, potentially due to oxidized bases, was also observed in non-irradiated XP-V cells, indicating that basal mutagenesis caused by oxidative stress may be related to internal tumours in XP-V patients. The low levels of mutations involving T induced by UVA indicate that pol eta is not responsible for correctly replicating T-containing pyrimidine dimers, a phenomenon known as the ‘A-rule’. Moreover, the mutation signature profile of UVA-irradiated XP-V cells is highly similar to the human skin cancer profile, revealing how studies involving cells deficient in DNA damage processing may be useful to understand the mechanisms of environmentally induced carcinogenesis. Oxford University Press 2020-02-28 2019-12-19 /pmc/articles/PMC7038989/ /pubmed/31853541 http://dx.doi.org/10.1093/nar/gkz1182 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/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 Genome Integrity, Repair and Replication
Moreno, Natália Cestari
de Souza, Tiago Antonio
Garcia, Camila Carrião Machado
Ruiz, Nathalia Quintero
Corradi, Camila
Castro, Ligia Pereira
Munford, Veridiana
Ienne, Susan
Alexandrov, Ludmil B
Menck, Carlos Frederico Martins
Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells
title Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells
title_full Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells
title_fullStr Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells
title_full_unstemmed Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells
title_short Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells
title_sort whole-exome sequencing reveals the impact of uva light mutagenesis in xeroderma pigmentosum variant human cells
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038989/
https://www.ncbi.nlm.nih.gov/pubmed/31853541
http://dx.doi.org/10.1093/nar/gkz1182
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