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The Multiple Cellular Roles of SMUG1 in Genome Maintenance and Cancer
Version 1
: Received: 23 January 2021 / Approved: 26 January 2021 / Online: 26 January 2021 (08:17:11 CET)
A peer-reviewed article of this Preprint also exists.
Raja, S.; Van Houten, B. The Multiple Cellular Roles of SMUG1 in Genome Maintenance and Cancer. Int. J. Mol. Sci. 2021, 22, 1981. Raja, S.; Van Houten, B. The Multiple Cellular Roles of SMUG1 in Genome Maintenance and Cancer. Int. J. Mol. Sci. 2021, 22, 1981.
Abstract
Single-stand selective monofunctional uracil DNA glycosylase 1 (SMUG1) works to remove uracil and certain oxidized bases from DNA during base excision repair (BER). This review provides a historical characterization of SMUG1 and 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) one important substrate of this enzyme. Biochemical and structural analyses provide remarkable insight into the mechanism of this glycosylase revealing SMUG1 has a unique helical wedge which influences damage recognition during repair. Rodent studies suggest that, while SMUG1 shares substrate specificity with another uracil glycosylase UNG2, loss of SMUG1 can have unique cellular phenotypes. This review highlights the multiple roles SMUG1 may play in preserving genome stability, and how the loss of SMUG1 activity may promote cancer. Finally, we discuss recent studies indicating SMUG1 has moonlighting functions beyond BER, playing a critical role in RNA processing including the RNA component of telomerase.
Keywords
DNA Damage; Base Excision Repair; SMUG1; 5-hmdU; Cancer
Subject
Biology and Life Sciences, Anatomy and Physiology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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