Decoding the base flipping mechanism of the SET- and RING-associated (SRA) domain of the epigenetic UHRF1 protein.

ABSTRACT: Ubiquitin-like, containing PHD and RING fingers domains 1 (UHRF1) plays a pivotal role in replicating DNA methylation patterns during cell division. Acting as a DNA reader, UHRF1, via its SET- and RING-associated (SRA) domain, recognizes hemi-methylated (HM) CpG sites and flips 5-methylcytosine (5mC) nucleobases. This flipping triggers DNA methyltransferase 1 (DNMT1) recruitment to methylate cytosine in the complementary strand. To investigate the SRA-induced base-flipping mechanism, we introduced thienoguanosine (thG), a fluorescent guanosine analogue, at four positions in HM and non-methylated duplexes. The interactions of these labelled duplexes with wild-type SRA and a G448D mutant (incapable of base-flipping) were monitored using a combination of stopped-flow fluorescence measurements

SUBMITTER: Mukherjee D 

PROVIDER: S-EPMC12448856 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature