2015
DOI: 10.1534/genetics.115.178566
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Lesion-Induced Mutation in the Hyperthermophilic Archaeon Sulfolobus acidocaldarius and Its Avoidance by the Y-Family DNA Polymerase Dbh

Abstract: Hyperthermophilic archaea offer certain advantages as models of genome replication, and Sulfolobus Y-family polymerases Dpo4 (S. solfataricus) and Dbh (S. acidocaldarius) have been studied intensively in vitro as biochemical and structural models of trans-lesion DNA synthesis (TLS). However, the genetic functions of these enzymes have not been determined in the native context of living cells. We developed the first quantitative genetic assays of replication past defined DNA lesions and error-prone motifs in Su… Show more

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Cited by 7 publications
(3 citation statements)
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References 66 publications
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“…As expected, the pol + recipient demonstrated the highest relative transformation efficiency (0.659), representing a limited impact of G oxidation on oligonucleotide incorporation and replication in normal cells. The corresponding transformation efficiency of the Δ dbh recipient strain was about 10% of this value (0.068), indicating that loss of the Y-family DNAP Dbh compromised the cell’s ability to tolerate oxidative damage, consistent with the biochemical and genetic properties of this DNAP ( Sakofsky et al, 2012 ; Sakofsky and Grogan, 2015 ; Jain et al, 2020 ). The triple polymerase mutant yielded a relative transformation efficiency similar to that of the Δdbh recipient.…”
Section: Resultsmentioning
confidence: 62%
“…As expected, the pol + recipient demonstrated the highest relative transformation efficiency (0.659), representing a limited impact of G oxidation on oligonucleotide incorporation and replication in normal cells. The corresponding transformation efficiency of the Δ dbh recipient strain was about 10% of this value (0.068), indicating that loss of the Y-family DNAP Dbh compromised the cell’s ability to tolerate oxidative damage, consistent with the biochemical and genetic properties of this DNAP ( Sakofsky et al, 2012 ; Sakofsky and Grogan, 2015 ; Jain et al, 2020 ). The triple polymerase mutant yielded a relative transformation efficiency similar to that of the Δdbh recipient.…”
Section: Resultsmentioning
confidence: 62%
“…Inactivation of the dbh gene in S. acidocaldarius does not change the overall spontaneous mutation rate, but the mutation spectrum changes significantly, with fewer insertion-deletion mutations and more base-substitution mutations [28]. Additional studies indicate that Dbh is primarily responsible for the accurate bypass of 8-oxo-dG lesions, by correctly inserting dC opposite the lesion up to 90% of the time, but does not increase the frequency of single base deletion mutations in a 5'-GY n repetitive sequence that would be a deletion hotspot in vitro [29].…”
Section: Introductionmentioning
confidence: 96%
“…Inactivation of the dbh gene in S. acidocaldarius does not change the overall spontaneous mutation rate, but the mutation spectrum changes significantly, with fewer insertion-deletion mutations and more base-substitution mutations [28]. Additional studies indicate that Dbh is primarily responsible for the accurate bypass of 8-oxo-dG lesions, by correctly inserting dC opposite the lesion up to 90% of the time, but does not increase the frequency of single base deletion mutations in a 5'-GY n repetitive sequence that would be a deletion hotspot in vitro [29].These findings suggest that Dbh is specifically recruited to sites of oxidative DNA damage and, because its access to replicating DNA is restricted, it does not introduce deletion mutations into the genome to the extent that the biochemical data would indicate. However, the intrinsic fidelity of Dbh may also increase in the cellular environment.…”
mentioning
confidence: 96%