Novel subcellular localization of the DNA helicase Twinkle at the kinetochore complex during mitosis in neuronal-like progenitor cells
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  • 作者:Martine Uittenbogaard ; Anne Chiaramello
  • 关键词:Chromosomal segregation ; Hexameric DNA helicases ; Kinetochore complex ; Mitochondria ; Mitosis ; Twinkle
  • 刊名:Histochemistry and Cell Biology
  • 出版年:2016
  • 出版时间:March 2016
  • 年:2016
  • 卷:145
  • 期:3
  • 页码:275-286
  • 全文大小:5,341 KB
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  • 作者单位:Martine Uittenbogaard (1)
    Anne Chiaramello (1)

    1. Department of Anatomy and Regenerative Biology, George Washington University Medical Center, 2300 I Street N.W., Washington, DC, 20037, USA
  • 刊物类别:Medicine
  • 刊物主题:Medicine & Public Health
    Anatomy
    Medicine/Public Health, general
  • 出版者:Springer Berlin / Heidelberg
  • ISSN:1432-119X
文摘
During mitosis, the kinetochore, a multi-protein structure located on the centromeric DNA, is responsible for proper segregation of the replicated genome. More specifically, the outer kinetochore complex component Ndc80/Hec1 plays a critical role in regulating microtubule attachment to the spindle for accurate sister chromatid segregation. In addition, DNA helicases play a key contribution for precise and complete disjunction of sister chromatids held together through double-stranded DNA catenations until anaphase. In this study, we focused our attention on the nuclear-encoded DNA helicase Twinkle, which functions as an essential helicase for replication of mitochondrial DNA. It regulates the copy number of the mitochondrial genome, while maintaining its integrity, two processes essential for mitochondrial biogenesis and bioenergetic functions. Although the majority of the Twinkle protein is imported into mitochondria, a small fraction remains cytosolic with an unknown function. In this study, we report a novel expression pattern of Twinkle during chromosomal segregation at distinct mitotic phases. By immunofluorescence microscopy, we found that Twinkle protein colocalizes with the outer kinetochore protein HEC1 as early as prophase until late anaphase in neuronal-like progenitor cells. Thus, our collective results have revealed an unexpected cell cycle-regulated expression pattern of the DNA helicase Twinkle, known for its role in mtDNA replication. Therefore, its recruitment to the kinetochore suggests an evolutionary conserved function for both mitochondrial and nuclear genomic inheritance.

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