No cancer predisposition or increased spontaneous mutation frequencies in NEIL DNA glycosylases-deficient mice

Abstract Base excision repair (BER) is a major pathway for removal of DNA base lesions and maintenance of genomic stability, which is essential in cancer prevention. DNA glycosylases recognize and remove specific lesions in the first step of BER. The existence of a number of these enzymes with overl...

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Autores principales:	Veslemøy Rolseth, Luisa Luna, Ann Karin Olsen, Rajikala Suganthan, Katja Scheffler, Christine G. Neurauter, Ying Esbensen, Anna Kuśnierczyk, Gunn A. Hildrestrand, Anne Graupner, Jill M. Andersen, Geir Slupphaug, Arne Klungland, Hilde Nilsen, Magnar Bjørås
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5c917068e02c43e0970c726380db6068
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spelling	oai:doaj.org-article:5c917068e02c43e0970c726380db60682021-12-02T16:06:04ZNo cancer predisposition or increased spontaneous mutation frequencies in NEIL DNA glycosylases-deficient mice10.1038/s41598-017-04472-42045-2322https://doaj.org/article/5c917068e02c43e0970c726380db60682017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04472-4https://doaj.org/toc/2045-2322Abstract Base excision repair (BER) is a major pathway for removal of DNA base lesions and maintenance of genomic stability, which is essential in cancer prevention. DNA glycosylases recognize and remove specific lesions in the first step of BER. The existence of a number of these enzymes with overlapping substrate specificities has been thought to be the reason why single knock-out models of individual DNA glycosylases are not cancer prone. In this work we have characterized DNA glycosylases NEIL1 and NEIL2 (Neil1 −/− /Neil2 −/−) double and NEIL1, NEIL2 and NEIL3 (Neil1 −/− /Neil2 −/− /Neil3 −/−) triple knock-out mouse models. Unexpectedly, our results show that these mice are not prone to cancer and have no elevated mutation frequencies under normal physiological conditions. Moreover, telomere length is not affected and there was no accumulation of oxidative DNA damage compared to wild-type mice. These results strengthen the hypothesis that the NEIL enzymes are not simply back-up enzymes for each other but enzymes that have distinct functions beyond canonical repair.Veslemøy RolsethLuisa LunaAnn Karin OlsenRajikala SuganthanKatja SchefflerChristine G. NeurauterYing EsbensenAnna KuśnierczykGunn A. HildrestrandAnne GraupnerJill M. AndersenGeir SlupphaugArne KlunglandHilde NilsenMagnar BjøråsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Veslemøy Rolseth Luisa Luna Ann Karin Olsen Rajikala Suganthan Katja Scheffler Christine G. Neurauter Ying Esbensen Anna Kuśnierczyk Gunn A. Hildrestrand Anne Graupner Jill M. Andersen Geir Slupphaug Arne Klungland Hilde Nilsen Magnar Bjørås No cancer predisposition or increased spontaneous mutation frequencies in NEIL DNA glycosylases-deficient mice
description	Abstract Base excision repair (BER) is a major pathway for removal of DNA base lesions and maintenance of genomic stability, which is essential in cancer prevention. DNA glycosylases recognize and remove specific lesions in the first step of BER. The existence of a number of these enzymes with overlapping substrate specificities has been thought to be the reason why single knock-out models of individual DNA glycosylases are not cancer prone. In this work we have characterized DNA glycosylases NEIL1 and NEIL2 (Neil1 −/− /Neil2 −/−) double and NEIL1, NEIL2 and NEIL3 (Neil1 −/− /Neil2 −/− /Neil3 −/−) triple knock-out mouse models. Unexpectedly, our results show that these mice are not prone to cancer and have no elevated mutation frequencies under normal physiological conditions. Moreover, telomere length is not affected and there was no accumulation of oxidative DNA damage compared to wild-type mice. These results strengthen the hypothesis that the NEIL enzymes are not simply back-up enzymes for each other but enzymes that have distinct functions beyond canonical repair.
format	article
author	Veslemøy Rolseth Luisa Luna Ann Karin Olsen Rajikala Suganthan Katja Scheffler Christine G. Neurauter Ying Esbensen Anna Kuśnierczyk Gunn A. Hildrestrand Anne Graupner Jill M. Andersen Geir Slupphaug Arne Klungland Hilde Nilsen Magnar Bjørås
author_facet	Veslemøy Rolseth Luisa Luna Ann Karin Olsen Rajikala Suganthan Katja Scheffler Christine G. Neurauter Ying Esbensen Anna Kuśnierczyk Gunn A. Hildrestrand Anne Graupner Jill M. Andersen Geir Slupphaug Arne Klungland Hilde Nilsen Magnar Bjørås
author_sort	Veslemøy Rolseth
title	No cancer predisposition or increased spontaneous mutation frequencies in NEIL DNA glycosylases-deficient mice
title_short	No cancer predisposition or increased spontaneous mutation frequencies in NEIL DNA glycosylases-deficient mice
title_full	No cancer predisposition or increased spontaneous mutation frequencies in NEIL DNA glycosylases-deficient mice
title_fullStr	No cancer predisposition or increased spontaneous mutation frequencies in NEIL DNA glycosylases-deficient mice
title_full_unstemmed	No cancer predisposition or increased spontaneous mutation frequencies in NEIL DNA glycosylases-deficient mice
title_sort	no cancer predisposition or increased spontaneous mutation frequencies in neil dna glycosylases-deficient mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5c917068e02c43e0970c726380db6068
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No cancer predisposition or increased spontaneous mutation frequencies in NEIL DNA glycosylases-deficient mice

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