Scientific reports · 2017
No cancer predisposition or increased spontaneous mutation frequencies in NEIL DNA glycosylases-deficient mice.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Rolseth Veslemøy, Luna Luisa, Olsen Ann Karin, Suganthan Rajikala, Scheffler Katja, Neurauter Christine G, Esbensen Ying, Kuśnierczyk Anna, Hildrestrand Gunn A, Graupner Anne, Andersen Jill M, Slupphaug Geir, Klungland Arne, Nilsen Hilde, Bjørås Magnar
Аннотация
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.