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Processing closely spaced lesions during Nucleotide Excision Repair triggers mutagenesis in E. coli
It is generally assumed that most point mutations are fixed when damage containing template DNA undergoes replication, either right at the fork or behind the fork during gap filling. Here we provide genetic evidence for a pathway, dependent on Nucleotide Excision Repair, that induces mutations when...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5521853/ https://www.ncbi.nlm.nih.gov/pubmed/28686598 http://dx.doi.org/10.1371/journal.pgen.1006881 |
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author | Janel-Bintz, Régine Napolitano, Rita L. Isogawa, Asako Fujii, Shingo Fuchs, Robert P. |
author_facet | Janel-Bintz, Régine Napolitano, Rita L. Isogawa, Asako Fujii, Shingo Fuchs, Robert P. |
author_sort | Janel-Bintz, Régine |
collection | PubMed |
description | It is generally assumed that most point mutations are fixed when damage containing template DNA undergoes replication, either right at the fork or behind the fork during gap filling. Here we provide genetic evidence for a pathway, dependent on Nucleotide Excision Repair, that induces mutations when processing closely spaced lesions. This pathway, referred to as Nucleotide Excision Repair-induced Mutagenesis (NERiM), exhibits several characteristics distinct from mutations that occur within the course of replication: i) following UV irradiation, NER-induced mutations are fixed much more rapidly (t ½ ≈ 30 min) than replication dependent mutations (t ½ ≈ 80–100 min) ii) NERiM specifically requires DNA Pol IV in addition to Pol V iii) NERiM exhibits a two-hit dose-response curve that suggests processing of closely spaced lesions. A mathematical model let us define the geometry (infer the structure) of the toxic intermediate as being formed when NER incises a lesion that resides in close proximity of another lesion in the complementary strand. This critical NER intermediate requires Pol IV / Pol II for repair, it is either lethal if left unrepaired or mutation-prone when repaired. Finally, NERiM is found to operate in stationary phase cells providing an intriguing possibility for ongoing evolution in the absence of replication. |
format | Online Article Text |
id | pubmed-5521853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55218532017-08-07 Processing closely spaced lesions during Nucleotide Excision Repair triggers mutagenesis in E. coli Janel-Bintz, Régine Napolitano, Rita L. Isogawa, Asako Fujii, Shingo Fuchs, Robert P. PLoS Genet Research Article It is generally assumed that most point mutations are fixed when damage containing template DNA undergoes replication, either right at the fork or behind the fork during gap filling. Here we provide genetic evidence for a pathway, dependent on Nucleotide Excision Repair, that induces mutations when processing closely spaced lesions. This pathway, referred to as Nucleotide Excision Repair-induced Mutagenesis (NERiM), exhibits several characteristics distinct from mutations that occur within the course of replication: i) following UV irradiation, NER-induced mutations are fixed much more rapidly (t ½ ≈ 30 min) than replication dependent mutations (t ½ ≈ 80–100 min) ii) NERiM specifically requires DNA Pol IV in addition to Pol V iii) NERiM exhibits a two-hit dose-response curve that suggests processing of closely spaced lesions. A mathematical model let us define the geometry (infer the structure) of the toxic intermediate as being formed when NER incises a lesion that resides in close proximity of another lesion in the complementary strand. This critical NER intermediate requires Pol IV / Pol II for repair, it is either lethal if left unrepaired or mutation-prone when repaired. Finally, NERiM is found to operate in stationary phase cells providing an intriguing possibility for ongoing evolution in the absence of replication. Public Library of Science 2017-07-07 /pmc/articles/PMC5521853/ /pubmed/28686598 http://dx.doi.org/10.1371/journal.pgen.1006881 Text en © 2017 Janel-Bintz et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Janel-Bintz, Régine Napolitano, Rita L. Isogawa, Asako Fujii, Shingo Fuchs, Robert P. Processing closely spaced lesions during Nucleotide Excision Repair triggers mutagenesis in E. coli |
title | Processing closely spaced lesions during Nucleotide Excision Repair triggers mutagenesis in E. coli |
title_full | Processing closely spaced lesions during Nucleotide Excision Repair triggers mutagenesis in E. coli |
title_fullStr | Processing closely spaced lesions during Nucleotide Excision Repair triggers mutagenesis in E. coli |
title_full_unstemmed | Processing closely spaced lesions during Nucleotide Excision Repair triggers mutagenesis in E. coli |
title_short | Processing closely spaced lesions during Nucleotide Excision Repair triggers mutagenesis in E. coli |
title_sort | processing closely spaced lesions during nucleotide excision repair triggers mutagenesis in e. coli |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5521853/ https://www.ncbi.nlm.nih.gov/pubmed/28686598 http://dx.doi.org/10.1371/journal.pgen.1006881 |
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