Cargando…
The interplay at the replisome mitigates the impact of oxidative damage on the genetic integrity of hyperthermophilic Archaea
8-oxodeoxyguanosine (8-oxodG), a major oxidised base modification, has been investigated to study its impact on DNA replication in hyperthermophilic Archaea. Here we show that 8-oxodG is formed in the genome of growing cells, with elevated levels following exposure to oxidative stress. Functional ch...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559790/ https://www.ncbi.nlm.nih.gov/pubmed/31184586 http://dx.doi.org/10.7554/eLife.45320 |
_version_ | 1783425863570685952 |
---|---|
author | Killelea, Tom Palud, Adeline Akcha, Farida Lemor, Mélanie L'haridon, Stephane Godfroy, Anne Henneke, Ghislaine |
author_facet | Killelea, Tom Palud, Adeline Akcha, Farida Lemor, Mélanie L'haridon, Stephane Godfroy, Anne Henneke, Ghislaine |
author_sort | Killelea, Tom |
collection | PubMed |
description | 8-oxodeoxyguanosine (8-oxodG), a major oxidised base modification, has been investigated to study its impact on DNA replication in hyperthermophilic Archaea. Here we show that 8-oxodG is formed in the genome of growing cells, with elevated levels following exposure to oxidative stress. Functional characterisation of cell-free extracts and the DNA polymerisation enzymes, PolB, PolD, and the p41/p46 complex, alone or in the presence of accessory factors (PCNA and RPA) indicates that translesion synthesis occurs under replicative conditions. One of the major polymerisation effects was stalling, but each of the individual proteins could insert and extend past 8-oxodG with differing efficiencies. The introduction of RPA and PCNA influenced PolB and PolD in similar ways, yet provided a cumulative enhancement to the polymerisation performance of p41/p46. Overall, 8-oxodG translesion synthesis was seen to be potentially mutagenic leading to errors that are reminiscent of dA:8-oxodG base pairing. |
format | Online Article Text |
id | pubmed-6559790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-65597902019-06-12 The interplay at the replisome mitigates the impact of oxidative damage on the genetic integrity of hyperthermophilic Archaea Killelea, Tom Palud, Adeline Akcha, Farida Lemor, Mélanie L'haridon, Stephane Godfroy, Anne Henneke, Ghislaine eLife Biochemistry and Chemical Biology 8-oxodeoxyguanosine (8-oxodG), a major oxidised base modification, has been investigated to study its impact on DNA replication in hyperthermophilic Archaea. Here we show that 8-oxodG is formed in the genome of growing cells, with elevated levels following exposure to oxidative stress. Functional characterisation of cell-free extracts and the DNA polymerisation enzymes, PolB, PolD, and the p41/p46 complex, alone or in the presence of accessory factors (PCNA and RPA) indicates that translesion synthesis occurs under replicative conditions. One of the major polymerisation effects was stalling, but each of the individual proteins could insert and extend past 8-oxodG with differing efficiencies. The introduction of RPA and PCNA influenced PolB and PolD in similar ways, yet provided a cumulative enhancement to the polymerisation performance of p41/p46. Overall, 8-oxodG translesion synthesis was seen to be potentially mutagenic leading to errors that are reminiscent of dA:8-oxodG base pairing. eLife Sciences Publications, Ltd 2019-06-11 /pmc/articles/PMC6559790/ /pubmed/31184586 http://dx.doi.org/10.7554/eLife.45320 Text en © 2019, Killelea et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Killelea, Tom Palud, Adeline Akcha, Farida Lemor, Mélanie L'haridon, Stephane Godfroy, Anne Henneke, Ghislaine The interplay at the replisome mitigates the impact of oxidative damage on the genetic integrity of hyperthermophilic Archaea |
title | The interplay at the replisome mitigates the impact of oxidative damage on the genetic integrity of hyperthermophilic Archaea |
title_full | The interplay at the replisome mitigates the impact of oxidative damage on the genetic integrity of hyperthermophilic Archaea |
title_fullStr | The interplay at the replisome mitigates the impact of oxidative damage on the genetic integrity of hyperthermophilic Archaea |
title_full_unstemmed | The interplay at the replisome mitigates the impact of oxidative damage on the genetic integrity of hyperthermophilic Archaea |
title_short | The interplay at the replisome mitigates the impact of oxidative damage on the genetic integrity of hyperthermophilic Archaea |
title_sort | interplay at the replisome mitigates the impact of oxidative damage on the genetic integrity of hyperthermophilic archaea |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559790/ https://www.ncbi.nlm.nih.gov/pubmed/31184586 http://dx.doi.org/10.7554/eLife.45320 |
work_keys_str_mv | AT killeleatom theinterplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea AT paludadeline theinterplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea AT akchafarida theinterplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea AT lemormelanie theinterplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea AT lharidonstephane theinterplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea AT godfroyanne theinterplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea AT hennekeghislaine theinterplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea AT killeleatom interplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea AT paludadeline interplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea AT akchafarida interplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea AT lemormelanie interplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea AT lharidonstephane interplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea AT godfroyanne interplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea AT hennekeghislaine interplayatthereplisomemitigatestheimpactofoxidativedamageonthegeneticintegrityofhyperthermophilicarchaea |