SSU72 RNA Polymerase II C-terminal domain (CTD) phosphatase is a dual-specificity phosphatase that plays a crucial role in the transcription cycle of RNA Polymerase II. This enzyme is responsible for dephosphorylating the serine residues at positions 5 and 7 of the heptapeptide repeats in the CTD of RNA Polymerase II. The human recombinant form of SSU72 has been extensively studied to understand its function and regulation in gene expression.
SSU72 was initially identified in Saccharomyces cerevisiae as an essential gene for cell viability . The enzyme is characterized by its ability to dephosphorylate both phosphoserine/threonine and phosphotyrosine residues, making it a dual-specificity phosphatase . The structure of SSU72 includes a catalytic domain that prefers the cis configuration of the serine-proline motif within its substrate .
The primary function of SSU72 is to regulate the phosphorylation status of the CTD of RNA Polymerase II during the transcription cycle . Phosphorylation of the CTD is a dynamic process that is essential for the initiation, elongation, and termination of transcription. SSU72 is involved in the dephosphorylation of Ser5 and Ser7 residues, which is critical for the transition between different stages of transcription .
SSU72 enters the transcription cycle during the formation of preinitiation complexes (PICs) and is physically associated with very early elongation complexes . The enzyme’s activity is regulated by various factors that influence its function during the transition between initiation and pausing . This regulation ensures that SSU72 can act on early transcription complexes and may also function in the PIC prior to initiation .
Beyond its role in transcription, SSU72 is involved in several other cellular processes. It regulates sister chromatid cohesion and the separation of duplicated chromosomes during the cell cycle . Additionally, SSU72 plays a role in T cell receptor signaling, telomere regulation, and hepatocyte homeostasis in response to stress and damage signals .