Polynucleotide kinase 3'-phosphatase (PNKP)

Polynucleotide kinase 3'-phosphatase (PNKP) is a bifunctional enzyme crucial for the repair of DNA strand breaks, responsible for catalyzing two key activities: addition of a phosphate group to 5'-hydroxyl termini and removal of a phosphate group from 3'-phosphate DNA ends[4][8]. These modifications are needed to generate the 5'-phosphate and 3'-hydroxyl termini required for subsequent action by DNA polymerases and ligases[1][4]. PNKP is essential in several DNA repair pathways, including non-homologous end-joining and base excision repair, operating in concert with other repair factors (such as XRCC1 and XRCC4), and is considered critical for maintaining genomic stability, particularly in neural tissue[4][8]. Mutations can cause neurodevelopmental syndromes, and PNKP function modulates cellular sensitivity to DNA-damaging agents, including cancer therapies[4][8][6]. Its activity is not known to be directly targeted by drugs in current clinical use, but its central role in DNA repair makes it of therapeutic interest, especially in oncology contexts[4][8].

Other names

polynucleotide kinase/phosphatasePNKPDNA 5'-kinase/3'-phosphatasebifunctional polynucleotide phosphatase/kinase

Catalyzes phosphorylation of DNA 5'-hydroxyl termini. Removes phosphate from DNA 3'-phosphate termini. Restores ligatable 5'-phosphate and 3'-hydroxyl ends for ligation and repair.