The Stewart Shuman Lab: Projects
RNA repair pathways rely on RNA ligases to maintain or manipulate RNA structure in response to biologically purposeful RNA cleavage events. The goal of this project is to illuminate the mechanisms and structures of enzymes that repair broken RNA ends.
DNA repair and replication pathways converge on a common final step in which the continuity of the repaired DNA strand is restored by DNA ligase, an enzyme that converts nicks into phosphodiester bonds. We aim to elucidate the structures and catalytic mechanisms of DNA ligases from diverse taxa, especially the basis for nick sensing.
The carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol2) consists of tandemly repeated heptapeptides of consensus sequence YSPTSPS. The CTD is essential for cell viability because it recruits proteins that regulate transcription, modify chromatin structure, and catalyze or regulate mRNA capping, splicing, and polyadenylation. The inherently plastic CTD structure is modulated by dynamic phosphorylation and dephosphorylation of the heptad serine (S2, S5, S7), threonine (T4), and tyrosine (Y1) residues. The phospho-status of the CTD provides informational cues about the transcription machinery – a “CTD code” – that is “read” by CTD receptor proteins. Our goals in this project are to understand how CTD information is inscribed, organized, and transduced to cellular effectors, and how the CTD code governs gene expression.