PDIP46 (DNA polymerase δ interacting protein 46) is an activating factor for human DNA polymerase δ

Oncotarget
Xiaoxiao WangMarietta Y W T Lee

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 in...Continue Reading

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Citations

Jul 25, 2017·Genes·Marietta Y W T LeeErnest Y C Lee
Aug 21, 2019·International Journal of Molecular Sciences·Víctor Jiménez-GonzálezAlbert García-Quintanilla
Jul 22, 2019·DNA Repair·Marietta Y W T LeeErnest Y C Lee
Feb 6, 2017·Molecular Cell·Katherine N Choe, George-Lucian Moldovan

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Methods Mentioned

BETA
two-hybrid
pull-down
immunoprecipitation
electrophoresis
pull-downs
ChIP
pull down
FRET
dissection
PCR

Software Mentioned

ImageQuant
Prism
BLAST

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