
Phosphorylation of PNKP at threonine 118 by CDKs is essential for its recruitment to single-strand DNA gaps between Okazaki fragments, allowing PNKP to process the ends and promote their ligation, thereby maintaining genome stability during DNA replication.


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Polynucleotide kinase phosphatase (PNKP) has enzymatic activities as 3′ -phosphatase and 5′ - kinase of DNA ends to promote DNA ligation and repair. Here, we show that cyclin-dependent kinases (CDKs) regulate the phosphorylation of threonine 118 (T118) in PNKP. This phosphorylation allows recruitment to the gapped DNA structure found in single-strand DNA nicks and/or gaps between Okazaki fragments (OFs) during DNA replication. T118A (alanine)-substituted PNKP-expressing cells exhibited accumulation of single-strand DNA gaps in S phase and accelerated replication fork progression. Furthermore, PNKP is involved in poly (ADP-ribose) polymerase 1 (PARP1)-dependent replication gap filling as a backup pathway in the absence of OFs ligation. Altogether, our data suggest that CDK-mediated PNKP phosphorylation at T118 is important for its recruitment to single-strand DNA gaps to proceed with OFs ligation and its backup errors via the gap-filling pathway to maintain genome stability.

### Competing Interest Statement

The authors have declared no competing interest.

CDKs-mediated phosphorylation of PNKP is required for end-processing of single-strand DNA gaps on Okazaki Fragments and genome stability

cyclin-dependent-kinase-phosphorylation-of-polynucleotide-kinase-phosphatase-promotes-okazaki-fragment-processing-and-genome-stability-during-dna-replication


Cyclin-Dependent Kinase Phosphorylation of Polynucleotide Kinase Phosphatase Promotes Okazaki Fragment Processing and Genome Stability During DNA Replication
