BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:"\;SMUG1 - A Classical DNA Glycosylase And An RNA Processing E nzyme"\; - Prof. Hilde Loge Nilsen\, The Institute of Clinical Medicin e\, Norway DTSTART:20171101T130000Z DTEND:20171101T140000Z UID:TALK88121@talks.cam.ac.uk CONTACT:Bobbie Claxton DESCRIPTION:Single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1) removes uracil and oxidized pyrimidines\, such as 5-hydroxymethy luracil\, via the Base Excision Repair (BER) pathway. \nEarly studies of S MUG1 function suggested that SMUG1 contributed little to repair of uracil in cells proficient for the UNG uracil-DNA glycosylase. I will present rec ent data from Ung-/-\, Smug1-/- and Ung/Smug1-double knockout mice that sh ow a synergistic increase in genomic uracil in the Ung/Smug1-double knocko ut compared to either single mutant [1]. This suggests that SMUG1 efficien tly prevents genomic uracil accumulation\, also in the presence of UNG. Wh ole genome sequencing of UNG/SMUG1-deficient tumours revealed that combine d UNG and SMUG1 deficiency leads to the accumulation of mutations\, primar ily C to T transitions within CpG sequences. \nIn addition to its classica l BER function\, SMUG1 interacts with Dyskerin 1 (DKC1) in nucleoli and Ca jal bodies and functions in RNA quality control [2]. Consequently\, Smug1- /- cells and tissues accumulate hmU in ribosomal RNA. As DKC1 is also a st ructural component of telomerase and promotes processing and in stabilizat ion of the human telomerase RNA component (TERC)\, we asked whether SMUG1 is required for telomere maintenance. I will present data that suggest SMU G1 may be involved TERC biogenesis.\n\n \nReferences:\n1. Alsoe\, L.\, et al.\, Uracil Accumulation and Mutagenesis Dominated by Cytosine Deaminatio n in CpG Dinucleotides in Mice Lacking UNG and SMUG1. Sci Rep\, 2017. 7(1) : p. 7199.\n2. Jobert\, L.\, et al.\, The human base excision repair enzym e SMUG1 directly interacts with DKC1 and contributes to RNA quality contro l. Mol Cell\, 2013. 49(2): p. 339-45.\n\n LOCATION:Babraham - The Cambridge Building\; Queen Edith Room END:VEVENT END:VCALENDAR