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dc.contributor.authorMeier, Bettina
dc.contributor.authorVolkova, Nadezda V.
dc.contributor.authorWang, Bin
dc.contributor.authorGonzález-Huici, Víctor
dc.contributor.authorBertolini, Simone
dc.contributor.authorCampbell, Peter J.
dc.contributor.authorGerstung, Moritz
dc.contributor.authorGartner, Anton
dc.date.accessioned2021-10-06T19:18:11Z
dc.date.available2021-10-06T19:18:11Z
dc.date.issued2021-10-06
dc.date.submitted2021-06-02
dc.identifier.otherpone-d-21-18200
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329054
dc.description.abstractIonizing 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.
dc.languageen
dc.publisherPublic Library of Science
dc.subjectResearch Article
dc.subjectBiology and life sciences
dc.subjectResearch and analysis methods
dc.subjectMedicine and health sciences
dc.titleC. elegans genome-wide analysis reveals DNA repair pathways that act cooperatively to preserve genome integrity upon ionizing radiation
dc.typeArticle
dc.date.updated2021-10-06T19:18:11Z
prism.issueIdentifier10
prism.publicationNamePLOS ONE
prism.volume16
dc.identifier.doi10.17863/CAM.76499
dcterms.dateAccepted2021-09-22
rioxxterms.versionofrecord10.1371/journal.pone.0258269
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Cotterill, Sue
dc.contributor.orcidGonzález-Huici, Víctor [0000-0002-6977-1060]
dc.contributor.orcidGartner, Anton [0000-0003-4639-9902]
dc.identifier.eissn1932-6203
pubs.funder-project-idIBS Institute for Basic Science (IBS-R022-A2-2021)
pubs.funder-project-idWellcome Trust (RG70175)
pubs.funder-project-idWorldwide Cancer Research (18-0644)


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