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C. elegans genome-wide analysis reveals DNA repair pathways that act cooperatively to preserve genome integrity upon ionizing radiation.

Published version
Peer-reviewed

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Type

Article

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Authors

Meier, Bettina 
Volkova, Nadezda V 
Wang, Bin 
González-Huici, Víctor  ORCID logo  https://orcid.org/0000-0002-6977-1060
Bertolini, Simone 

Abstract

Ionizing radiation (IR) is widely used in cancer therapy and accidental or environmental exposure is a major concern. However, little is known about the genome-wide effects IR exerts on germ cells and the relative contribution of DNA repair pathways for mending IR-induced lesions. Here, using C. elegans as a model system and using primary sequencing data from our recent high-level overview of the mutagenic consequences of 11 genotoxic agents, we investigate in detail the genome-wide mutagenic consequences of exposing wild-type and 43 DNA repair and damage response defective C. elegans strains to a Caesium (Cs-137) source, emitting γ-rays. Cs-137 radiation induced single nucleotide variants (SNVs) at a rate of ~1 base substitution per 3 Gy, affecting all nucleotides equally. In nucleotide excision repair mutants, this frequency increased 2-fold concurrently with increased dinucleotide substitutions. As observed for DNA damage induced by bulky DNA adducts, small deletions were increased in translesion polymerase mutants, while base changes decreased. Structural variants (SVs) were augmented with dose, but did not arise with significantly higher frequency in any DNA repair mutants tested. Moreover, 6% of all mutations occurred in clusters, but clustering was not significantly altered in any DNA repair mutant background. Our data is relevant for better understanding how DNA repair pathways modulate IR-induced lesions.

Description

Keywords

Animals, Caenorhabditis elegans, Cisplatin, DNA Repair, Genome, Helminth, Humans, Mutation, Neoplasms, Polymorphism, Single Nucleotide, Radiation, Ionizing, Ultraviolet Rays

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

16

Publisher

Public Library of Science (PLoS)
Sponsorship
IBS Institute for Basic Science (IBS-R022-A2-2021)
Worldwide Cancer Research (18-0644)
Wellcome Trust (RG70175, 090944/Z/09/Z)