title: Further characterization of human DNA polymerase delta interacting protein 38.
abstract: Polymerase delta interacting protein 38 (PDIP38) was identified as a human DNA polymerase (pol) delta interacting protein through a direct interaction with p50, the small subunit of human pol delta. PDIP38 was also found to interact with proliferating cell nuclear antigen, which suggested that it might play a role in vivo in the processes of DNA replication and DNA repair in the nucleus. In order to characterize further this novel protein, we have examined its subcellular localization by the use of immunochemical and cellular fractionation techniques. These studies show that PDIP38 is a novel mitochondrial protein and is localized mainly to the mitochondria. PDIP38 was shown to possess a functional mitochondrial targeting sequence that is located within the first 35 N-terminal amino acid residues. The mature PDIP38 protein is about 50 amino acid residues smaller than the full-length precursor PDIP38 protein, consistent with it being processed by cleavage of the mitochondrial targeting sequence during entry into the mitochondria. His-tagged mature PDIP38 inhibited pol delta activity in vitro and interacted with human papillomavirus 16 E7 oncoprotein, suggesting that PDIP38 might play a role in the pol delta-mediated viral DNA replication. Although the localization of PDIP38 to the mitochondria suggests that it serves functions within the mitochondria, we cannot eliminate the possibility that it may be involved in pol delta-mediated DNA replication or DNA repair under certain conditions such as viral infection.
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Xie
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Suqing
authors.initials: S
authors.lastname: Xie
authors.forename: Amal
authors.initials: A
authors.lastname: Rahmeh
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.forename: Marietta Y W T
authors.initials: MY
authors.lastname: Lee
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004258:DNA Polymerase III / Q000737:chemistry* / Q000378:metabolism; D004260:DNA Repair; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D050725:Papillomavirus E7 Proteins; D010455:Peptides / Q000737:chemistry; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection
chemical_list: D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; C473592:POLDIP2 protein, human; D050725:Papillomavirus E7 Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D005982:Glutathione Transferase; D004258:DNA Polymerase III; D004259:DNA-Directed DNA Polymerase