PNKP Rabbit Polyclonal Antibody

PNKP, which stands for polynucleotide kinase 3'-phosphatase, is an enzyme that plays a significant role in various biological processes, including DNA replication, transcription, and RNA splicing. It is particularly crucial for the repair of DNA strand breaks, participating in both the repair of oxidized DNA bases and the response to DNA damage induced by agents such as ionizing radiation. PNKP possesses both 5′-kinase and 3′-phosphatase activities, which are essential for the phosphorylation of 5′-hydroxyl and removal of 3′-phosphate DNA strand break terminii. The regulation of PNKP is important, as demonstrated by the sensitivity to DNA damaging agents observed in cells with reduced PNKP levels. Furthermore, PNKP's cellular levels are regulated by an E3 ubiquitin ligase complex, which targets the protein for degradation. However, under oxidative stress conditions, phosphorylation of PNKP by protein kinase ATM inhibits this ubiquitylation-dependent degradation, leading to increased PNKP protein levels required for DNA repair. Mutations in the PNKP have been associated with autosomal recessive disorders characterized by severe neurological abnormalities, such as microcephaly, early-onset seizures, and developmental delay.