dc.contributor.author | Alsøe, Lene | |
dc.contributor.author | Sarno, Antonio | |
dc.contributor.author | Carracedo Huroz, Sergio | |
dc.contributor.author | Domanska, Diana Ewa | |
dc.contributor.author | Dingler, Felix | |
dc.contributor.author | Lirussi, Lisa | |
dc.contributor.author | Sengupta, Tanima | |
dc.contributor.author | Tekin, Nuriye Basdag | |
dc.contributor.author | Jobert, Laure | |
dc.contributor.author | Alexandrov, Ludmil B. | |
dc.contributor.author | Galashevskaya, Anastasia | |
dc.contributor.author | Rada, Cristina | |
dc.contributor.author | Sandve, Geir Kjetil | |
dc.contributor.author | Rognes, Torbjørn | |
dc.contributor.author | Krokan, Hans Einar | |
dc.contributor.author | Nilsen, Hilde Loge | |
dc.date.accessioned | 2018-02-09T11:43:12Z | |
dc.date.available | 2018-02-09T11:43:12Z | |
dc.date.created | 2017-10-24T10:38:58Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Scientific Reports. 2017, 7 (1). | nb_NO |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://hdl.handle.net/11250/2483697 | |
dc.description.abstract | Both 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. | nb_NO |
dc.language.iso | eng | nb_NO |
dc.publisher | Nature Publishing Group | nb_NO |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Uracil Accumulation and Mutagenesis Dominated by Cytosine Deamination in CpG Dinucleotides in Mice Lacking UNG and SMUG | nb_NO |
dc.type | Journal article | nb_NO |
dc.type | Peer reviewed | nb_NO |
dc.description.version | publishedVersion | nb_NO |
dc.source.pagenumber | 14 | nb_NO |
dc.source.volume | 7 | nb_NO |
dc.source.journal | Scientific Reports | nb_NO |
dc.source.issue | 1 | nb_NO |
dc.identifier.doi | 10.1038/s41598-017-07314-5 | |
dc.identifier.cristin | 1507132 | |
dc.relation.project | Notur/NorStore: NN9383K | nb_NO |
dc.relation.project | Notur/NorStore: NS9065K | nb_NO |
dc.description.localcode | © The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | nb_NO |
cristin.unitcode | 194,65,15,0 | |
cristin.unitname | Institutt for klinisk og molekylær medisin | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |