Polymerase delta-interacting protein 2 (POLDIP2)

Polymerase delta-interacting protein 2 (POLDIP2) is a multifunctional adaptor protein found in both the nucleus and mitochondria, encoded by the POLDIP2 gene on human chromosome 17q11.2[4][5]. It interacts with DNA polymerase delta (particularly the p50 subunit), proliferating cell nuclear antigen (PCNA), and several other specialized DNA polymerases (e.g., Pol η, Pol ζ, Pol λ, and PrimPol), thereby regulating DNA replication, DNA repair, and translesion synthesis (TLS)[1][3][5]. POLDIP2 also modulates responsiveness to oxidative DNA damage, partly through its interaction with NOX4 and its role in the generation and tolerance of reactive oxygen species (ROS)[1][2][5]. In mitochondria, it regulates key enzymes of energy metabolism (such as pyruvate dehydrogenase and α-ketoglutarate dehydrogenase) via effects on protein lipoylation[2]. Beyond its essential roles in genome stability, POLDIP2 is implicated in cell signaling pathways involved in cell migration, cytoskeletal regulation, and diseases such as cancer, cardiovascular disease, and neurodegenerative disorders like Alzheimer’s disease[5]. It is considered a key node for integrating metabolic, oxidative, and DNA damage responses, but no approved drugs target POLDIP2 directly[5].

Other names

Polymerase delta-interacting protein 2PDIP38POLD4HSPC017p38DKFZP586F152438 kDa DNA polymerase delta interaction proteinpolymerase (DNA) delta interacting protein 2polymerase (DNA-directed), delta interacting protein 2polymerase delta interacting protein 38