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dc.date.accessioned2018-02-14T17:11:53Z
dc.date.available2018-02-14T17:11:53Z
dc.date.created2017-10-24T10:38:58Z
dc.date.issued2017
dc.identifier.citationAlsøe, Lene Sarno, Antonio Carracedo Huroz, Sergio Domanska, Diana Ewa Dingler, Felix Lirussi, Lisa Sengupta, Tanima Tekin, Nuriye Basdag Jobert, Laure Alexandrov, Ludmil B. Galashevskaya, Anastasia Rada, Cristina Sandve, Geir Kjetil Rognes, Torbjørn Krokan, Hans Einar Nilsen, Hilde Loge . Uracil Accumulation and Mutagenesis Dominated by Cytosine Deamination in CpG Dinucleotides in Mice Lacking UNG and SMUG. Scientific Reports. 2017, 7(1)
dc.identifier.urihttp://hdl.handle.net/10852/60099
dc.description.abstractBoth a DNA lesion and an intermediate for antibody maturation, uracil is primarily processed by base excision repair (BER), either initiated by uracil-DNA glycosylase (UNG) or by single-strand selective monofunctional uracil DNA glycosylase (SMUG1). The relative in vivo contributions of each glycosylase remain elusive. To assess the impact of SMUG1 deficiency, we measured uracil and 5-hydroxymethyluracil, another SMUG1 substrate, in Smug1−/− mice. We found that 5-hydroxymethyluracil accumulated in Smug1−/− tissues and correlated with 5-hydroxymethylcytosine levels. The highest increase was found in brain, which contained about 26-fold higher genomic 5-hydroxymethyluracil levels than the wild type. Smug1−/− mice did not accumulate uracil in their genome and Ung−/− mice showed slightly elevated uracil levels. Contrastingly, Ung−/−Smug1−/− mice showed a synergistic increase in uracil levels with up to 25-fold higher uracil levels than wild type. Whole genome sequencing of UNG/SMUG1-deficient tumours revealed that combined UNG and SMUG1 deficiency leads to the accumulation of mutations, primarily C to T transitions within CpG sequences. This unexpected sequence bias suggests that CpG dinucleotides are intrinsically more mutation prone. In conclusion, we showed that SMUG1 efficiently prevent genomic uracil accumulation, even in the presence of UNG, and identified mutational signatures associated with combined UNG and SMUG1 deficiency.en_US
dc.languageEN
dc.language.isoenen_US
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleUracil Accumulation and Mutagenesis Dominated by Cytosine Deamination in CpG Dinucleotides in Mice Lacking UNG and SMUGen_US
dc.typeJournal articleen_US
dc.creator.authorAlsøe, Lene
dc.creator.authorSarno, Antonio
dc.creator.authorCarracedo Huroz, Sergio
dc.creator.authorDomanska, Diana Ewa
dc.creator.authorDingler, Felix
dc.creator.authorLirussi, Lisa
dc.creator.authorSengupta, Tanima
dc.creator.authorTekin, Nuriye Basdag
dc.creator.authorJobert, Laure
dc.creator.authorAlexandrov, Ludmil B.
dc.creator.authorGalashevskaya, Anastasia
dc.creator.authorRada, Cristina
dc.creator.authorSandve, Geir Kjetil
dc.creator.authorRognes, Torbjørn
dc.creator.authorKrokan, Hans Einar
dc.creator.authorNilsen, Hilde Loge
cristin.unitcode185,53,82,10
cristin.unitnameAvdeling for klinisk molekylærbiologi
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1507132
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Scientific Reports&rft.volume=7&rft.spage=&rft.date=2017
dc.identifier.jtitleScientific Reports
dc.identifier.volume7
dc.identifier.issue1
dc.identifier.pagecount14
dc.identifier.doihttp://dx.doi.org/10.1038/s41598-017-07314-5
dc.identifier.urnURN:NBN:no-62778
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn2045-2322
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/60099/1/uracil.pdf
dc.type.versionPublishedVersion
cristin.articleid7199
dc.relation.projectNOTUR/NORSTORE/NN9383K
dc.relation.projectNOTUR/NORSTORE/NS9065K


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