Next Article in Journal
EFR-Mediated Innate Immune Response in Arabidopsis thaliana is a Useful Tool for Identification of Novel ERQC Modulators
Next Article in Special Issue
Functional Comparison of XPF Missense Mutations Associated to Multiple DNA Repair Disorders
Previous Article in Journal
RNA Editors, Cofactors, and mRNA Targets: An Overview of the C-to-U RNA Editing Machinery and Its Implication in Human Disease
Previous Article in Special Issue
Mechanisms of DNA Damage Tolerance: Post-Translational Regulation of PCNA
Open AccessArticle

Stimulation of Replication Template-Switching by DNA-Protein Crosslinks

Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454-9110, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Genes 2019, 10(1), 14; https://doi.org/10.3390/genes10010014
Received: 31 October 2018 / Revised: 10 December 2018 / Accepted: 12 December 2018 / Published: 27 December 2018
(This article belongs to the Special Issue Chromosome Replication and Genome Integrity)
Covalent DNA protein crosslinks (DPCs) are common lesions that block replication. We examine here the consequence of DPCs on mutagenesis involving replicational template-switch reactions in Escherichia coli. 5-Azacytidine (5-azaC) is a potent mutagen for template-switching. This effect is dependent on DNA cytosine methylase (Dcm), implicating the Dcm-DNA covalent complex trapped by 5-azaC as the initiator for mutagenesis. The leading strand of replication is more mutable than the lagging strand, which can be explained by blocks to the replicative helicase and/or fork regression. We find that template-switch mutagenesis induced by 5-azaC does not require double strand break repair via RecABCD; the ability to induce the SOS response is anti-mutagenic. Mutants in recB, but not recA, exhibit high constitutive rates of template-switching, and we suggest that RecBCD-mediated DNA degradation prevents template-switching associated with fork regression. A mutation in the DnaB fork helicase also promotes high levels of template-switching. We also find that other DPC-inducers, formaldehyde (a non-specific crosslinker) and ciprofloxacin (a topoisomerase II poison) are also strong mutagens for template-switching with similar genetic properties. Induction of mutations and genetic rearrangements that occur by template-switching may constitute a previously unrecognized component of the genotoxicity and genetic instability promoted by DPCs. View Full-Text
Keywords: DNA replication; DNA repair; genetic recombination; mutagenesis DNA replication; DNA repair; genetic recombination; mutagenesis
Show Figures

Graphical abstract

MDPI and ACS Style

Laranjo, L.T.; Klaric, J.A.; Pearlman, L.R.; Lovett, S.T. Stimulation of Replication Template-Switching by DNA-Protein Crosslinks. Genes 2019, 10, 14.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map

1
Back to TopTop