title: PDIP46 (DNA polymerase δ interacting protein 46) is an activating factor for human DNA polymerase δ.
abstract: PDIP46 (SKAR, POLDIP3) was discovered through its interaction with the p50 subunit of human DNA polymerase δ (Pol δ). Its functions in DNA replication are unknown. PDIP46 associates with Pol δ in cell extracts both by immunochemical and protein separation methods, as well as by ChIP analyses. PDIP46 also interacts with PCNA via multiple copies of a novel PCNA binding motif, the APIMs (AlkB homologue-2 PCNA-Interacting Motif). Sites for both p50 and PCNA binding were mapped to the N-terminal region containing the APIMs. Functional assays for the effects of PDIP46 on Pol δ activity on singly primed ssM13 DNA templates revealed that it is a novel and potent activator of Pol δ. The effects of PDIP46 on Pol δ in primer extension, strand displacement and synthesis through simple hairpin structures reveal a mechanism where PDIP46 facilitates Pol δ4 synthesis through regions of secondary structure on complex templates. In addition, evidence was obtained that PDIP46 is also capable of exerting its effects by a direct interaction with Pol δ, independent of PCNA. Mutation of the Pol δ and PCNA binding region resulted in a loss of PDIP46 functions. These studies support the view that PDIP46 is a novel accessory protein for Pol δ that is involved in cellular DNA replication. This raises the possibility that altered expression of PDIP46 or its mutation may affect Pol δ functions in vivo, and thereby be a nexus for altered genomic stability.
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA.
authors.forename: Sufang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA.
authors.forename: Fu
authors.initials: F
authors.lastname: Yue
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA.
authors.forename: Szu Hua Sharon
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA.
authors.forename: Amal A
authors.initials: AA
authors.lastname: Rahmeh
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA.
authors.forename: Ernest Y C
authors.initials: EY
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA.
authors.forename: Zhongtao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA.
authors.forename: Marietta Y W T
authors.initials: MY
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D004258:DNA Polymerase III / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004789:Enzyme Activation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; C495327:POLDIP3 protein, human; D016601:RNA-Binding Proteins; D004258:DNA Polymerase III
keywords: DNA polymerase δ; DNA replication; PDIP46; POLDIP3; SKAR
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