Rabbit Anti-Human SPRTN (N-terminal) Polyclonal antibody

This perspective aims to discuss the potential physiological roles and regulation mechanisms of the recently identified Candida albicans Wss1 protease important in DNA-protein crosslink (DPC) tolerance and repair. DPC is a bulky DNA lesion that blocks essential DNA transactions; thus, it poses a significant threat to genome integrity if left unrepaired. Discoveries of Wss1 in Saccharomyces cerevisiae and SPRTN in human as DPC proteases have demonstrated the importance of protease function in DPC repair. Our recent study revealed that Wss1 in C. albicans, an opportunistic pathogen that can cause life-threatening infection in immunocompromised individuals, also promotes DPC tolerance similarly to both S. cerevisiae Wss1 and human SPRTN. However, its molecular mechanism and regulation are still poorly understood. Here, we briefly discuss the recent insights into C. albicans Wss1 based on the information from S. cerevisiae, as well as outline the aspect of this protein that could make it a potential target for antifungal drug development.

Covalent DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription. Little was known about DPC-specific repair mechanisms until the recent identification of a DPC-processing protease in yeast. The existence of a DPC protease in higher eukaryotes is inferred from data in Xenopus laevis egg extracts, but its identity remains elusive. Here we identify the metalloprotease SPRTN as the DPC protease acting in metazoans. Loss of SPRTN results in failure to repair DPCs and hypersensitivity to DPC-inducing agents. SPRTN accomplishes DPC processing through a unique DNA-induced protease activity, which is controlled by several sophisticated regulatory mechanisms. Cellular, biochemical, and structural studies define a DNA switch triggering its protease activity, a ubiquitin switch controlling SPRTN chromatin accessibility, and regulatory autocatalytic cleavage. Our data also provide a molecular explanation on how SPRTN deficiency causes the premature aging and cancer predisposition disorder Ruijs-Aalfs syndrome.