The finger loop of the SRA domain in the E3 ligase UHRF1 is a regulator of ubiquitin targeting and is required for the maintenance of DNA methylation.

ABSTRACT: The Su(var)3-9, enhancer of zeste, and trithorax (SET) and really interesting new gene (RING) finger-associated (SRA) protein domain is conserved across bacteria and eukaryota and coordinates extrahelical or "flipped" DNA bases. A functional SRA domain is required for ubiquitin-like with PHD and RING finger domains 1 (UHRF1) E3 ubiquitin ligase activity toward histone H3, a mechanism for recruiting the DNA methylation maintenance enzyme DNA methyltransferase 1 (DNMT1). The SRA domain supports UHRF1 oncogenic activity in colon cancer cells, highlighting that UHRF1 SRA antagonism could be a cancer therapeutic strategy. Here we used molecular dynamics simulations, DNA binding assays, in vitro ubiquitination reactions, and DNA methylation analysis to identify the SRA finger loop as a re

SUBMITTER: Vaughan RM 

PROVIDER: S-EPMC6816099 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature