Single-strand selective monofunctional uracil DNA glycosylase (SMUG1) (SMUG1)

Single-strand selective monofunctional uracil DNA glycosylase (SMUG1) is a key enzyme in the base excision repair (BER) pathway, primarily responsible for the removal of uracil from DNA to prevent mutations [UniProt: P57786]. While it was initially identified for its activity on single-stranded DNA, it is also highly efficient at repairing double-stranded DNA and uniquely processes oxidized bases like 5-hydroxymethyluracil (5-hmU) [PMID: 11328882]. In clinical oncology, SMUG1 is recognized for its role in mediating resistance to fluoropyrimidine-based chemotherapies, such as 5-fluorouracil (5-FU), by repairing the drug-induced DNA damage [PMID: 21856230]. Consequently, SMUG1 is considered a promising therapeutic target for chemosensitization, as its inhibition can lead to the accumulation of lethal DNA lesions in tumor cells. Beyond cancer, SMUG1's role in maintaining genomic integrity links it to processes of aging and the prevention of various genetic disorders [NCBI Gene: 23583]. Current research focuses on developing small-molecule inhibitors to enhance the efficacy of existing DNA-damaging agents.

Other names

SMUG1Single-strand selective monofunctional uracil-DNA glycosylase 1HMUDGUNG3

Inhibition of SMUG1 enzymatic activity prevents the excision of uracil and fluorinated bases from DNA, leading to the accumulation of DNA lesions, strand breaks, and subsequent cell death in rapidly dividing cancer cells [PMID: 21856230].