SMUG1 but not UNG DNA glycosylase contributes to the cellular response to recovery from 5-fluorouracil induced replication stress.

ABSTRACT: 5-Fluorouracil (5-FU) is a widely utilized cancer chemotherapeutic that causes DNA damage via two mechanisms. Its active metabolite inhibits thymidylate synthase, which deprives cells of TTP and causes the introduction of uracil in DNA. Also, 5-FU is directly incorporated into DNA. Both uracil and 5-FU in DNA are recognized by uracil-DNA glycosylases (UDGs), which initiate base excision repair. UNG and SMUG1 are the two human UDGs most likely to combat the genomic incorporation of uracil and 5-FU during replication. In this study, we examined the roles of UNG and SMUG1 in the initial cellular response to 5-FU and compared continuous exposure to a 24h exposure followed by incubation in drug-free media, which mimics what occurs clinically. Loss of UNG did not alter cellular sensitivity to 5-

SUBMITTER: Nagaria P 

PROVIDER: S-EPMC3616158 | biostudies-literature | 2013 Mar-Apr

REPOSITORIES: biostudies-literature