The interplay at the replisome mitigates the impact of oxidative damage on the genetic integrity of hyperthermophilic Archaea

Type Article
Date 2019-06
Language English
Author(s) Killelea Tom3, Palud Adeline1, Akcha Farida2, Lemor Mélanie3, L'Haridon Stephane3, Godfroy AnneORCID1, Henneke GhislaineORCID1
Affiliation(s) 1 : Univ Brest, Ifremer, CNRS, Laboratoire de Microbiologie des Environnements Extrêmes, Plouzané, France
2 : Laboratoire d'Ecotoxicologie, Ifremer, Nantes, France
3 : Univ Brest, Ifremer, CNRS, Laboratoire de Microbiologie des Environnements Extrêmes, Plouzané, France
Source Elife (2050-084X) (eLife Sciences Publications, Ltd), 2019-06 , Vol. 8 , P. e45320. (20p.)
DOI 10.7554/eLife.45320
WOS© Times Cited 5
Abstract

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.

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Killelea Tom, Palud Adeline, Akcha Farida, Lemor Mélanie, L'Haridon Stephane, Godfroy Anne, Henneke Ghislaine (2019). The interplay at the replisome mitigates the impact of oxidative damage on the genetic integrity of hyperthermophilic Archaea. Elife, 8, e45320. (20p.). Publisher's official version : https://doi.org/10.7554/eLife.45320 , Open Access version : https://archimer.ifremer.fr/doc/00502/61372/