Events Associated with DNA Replication Disruption Are Not Observed in Hydrogen Peroxide-Treated Escherichia Coli

Authors

Chettar A. Hoff, Portland State University
Sierra S. Schmidt, Portland State University
Brandy J. Hackert, Portland State University
Travis K. Worley, Portland State University
Justin Courcelle, Portland State UniversityFollow
Charmain Courcelle, Portland State UniversityFollow

Sponsor

This study was supported by National Science Foundation grant MCB1916625.

Published In

G3-Genes Genomes Genetics

Document Type

Article

Publication Date

4-1-2021

Subjects

DNA replication -- Genomes

Abstract

UV irradiation induces pyrimidine dimers that block polymerases and disrupt the replisome. Restoring replication depends on the recF pathway proteins which process and maintain the replication fork DNA to allow the lesion to be repaired before replication resumes. Oxidative DNA lesions, such as those induced by hydrogen peroxide (H₂O₂), are often thought to require similar processing events, yet far less is known about how cells process oxidative damage during replication. Here we show that replication is not disrupted by H₂O₂-induced DNA damage in vivo. Following an initial inhibition, replication resumes in the absence of either lesion removal or RecF-processing. Restoring DNA synthesis depends on the presence of manganese in the medium, which we show is required for replication, but not repair to occur. The results demonstrate that replication is enzymatically inactivated, rather than physically disrupted by H₂O₂-induced DNA damage; indicate that inactivation is likely caused by oxidation of an iron-dependent replication or replication-associated protein that requires manganese to restore activity and synthesis; and address a long standing paradox as to why oxidative glycosylase mutants are defective in repair, yet not hypersensitive to H₂O₂. The oxygen-sensitive pausing may represent an adaptation that prevents replication from occurring under potentially lethal or mutagenic conditions.

Rights

© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America. 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 reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Locate the Document

https://doi.org/10.1093/g3journal/jkab044

DOI

10.1093/g3journal/jkab044

Persistent Identifier

https://archives.pdx.edu/ds/psu/35656

Citation Details

Hoff, C. A., Schmidt, S. S., Hackert, B. J., Worley, T. K., Courcelle, J., & Courcelle, C. T. (2021). Events associated with DNA replication disruption are not observed in hydrogen peroxide-treated Escherichia coli. G3 Genes|Genomes|Genetics, 11(4), jkab044. https://doi.org/10.1093/g3journal/jkab044