The disordered negatively charged C-terminus of the large HECT E3 ubiquitin ligase HERC2 provides structural and thermal stability to the HECT C-lobe.

Homologous to the C-terminus of E6AP (HECT) and RCC1-like domain (RLD)-containing protein 2 (HERC2) is a large, 528 kDa E3 ubiquitin ligase that is associated with cancer, oculocutaneous albanism type 2, Prader-Willi syndrome, and other neurological diseases. HERC2 has been found to contribute to double-stranded DNA break repairs, tumor suppression, maintaining centrosome architecture, and ubiquitylation. The C-terminal portion of the HECT domain (C-lobe) of HERC2 is responsible for transferring ubiquitin to a substrate but the precise function of the other eight domains in HERC2 are unknown.

Improved cytosine base editors generated from TadA variants.

Cytosine base editors (CBEs) enable programmable genomic C·G-to-T·A transition mutations and typically comprise a modified CRISPR-Cas enzyme, a naturally occurring cytidine deaminase, and an inhibitor of uracil repair. Previous studies have shown that CBEs utilizing naturally occurring cytidine deaminases may cause unguided, genome-wide cytosine deamination. While improved CBEs that decrease stochastic genome-wide off-targets have subsequently been reported, these editors can suffer from suboptimal on-target performance.