CDK-dependent phosphorylation regulates PNKP function in DNA replication.

ABSTRACT: Okazaki fragment maturation (OFM) stands as a pivotal DNA metabolic process, crucial for genome integrity and cell viability. Dysregulation of OFM leads to DNA single-strand breaks-accumulation, which is linked to various human diseases such as cancer and neurodegenerative disorders. Recent studies have implicated LIG3-XRCC1 acting in an alternative OFM pathway to the canonical FEN1-LIG1 pathway. Here, we reveal that polynucleotide kinase-phosphatase (PNKP) is another key participant in DNA replication, akin to LIG3-XRCC1. Through functional experiments, we demonstrate PNKP's enrichment at DNA replication forks and its association with PCNA, indicating its involvement in DNA replication processes. Cellular depletion of PNKP mirrors defects observed in OFM-related proteins, highlighting its

SUBMITTER: Mashayekhi F 

PROVIDER: S-EPMC11650725 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature