Mechanistic analysis of PrimPol regulation for maintenance of the human mitochondrial genome Kazutoshi Kasho, Timothee Laurent, Gorazd Stojkovic, Sjoerd Wanrooij Department of Medical Biochemistry and Biophysics, Umeå University, Sweden
The eukaryotic PrimPol protein is an unique enzyme which has both primase and polymerase activities. Besides its nuclear localization, human PrimPol is also localized in mitochondria where its functions to maintain the quality of mitochondrial genome DNA (mtDNA) (Torregrosa-MunÞumer et al, 2017 PNAS). The mechanism behind the mitochondrial targeting of PrimPol has remained elusive. Also, the processivity of PrimPol is very low, and therefore it is likely that unknown factor(s) might regulate the PrimPol localization and activity in vivo. In this study we focus on the PrimPol-interacting protein PolDIP2 (polymerase delta-interacting protein 2). Similar to PrimPol, PolDIP2 has a dual localization and previous study suggested that PolDIP2 can stimulate the polymerase activity of PrimPol (Guilliam et al, 2016 NAR), however, the mechanism by which this stimulation occurs remains unclear. In this study, we analyze the mechanism by which PolDIP2 regulates PrimPol using biochemical methods, and will discuss the role of PolDIP2 in maintaining the mtDNA quality in human cells.
Funding This study is supported by the Overseas Research Fellowships from the Japan Society for the Promotion of Science (JSPS) (K.K.).
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