title: Novel subcellular localization of the DNA helicase Twinkle at the kinetochore complex during mitosis in neuronal-like progenitor cells.
abstract: 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.
authors.affiliation: Department of Anatomy and Regenerative Biology, George Washington University Medical Center, 2300 I Street N.W., Washington, DC, 20037, USA.
authors.forename: Martine
authors.initials: M
authors.lastname: Uittenbogaard
authors.affiliation: Department of Anatomy and Regenerative Biology, George Washington University Medical Center, 2300 I Street N.W., Washington, DC, 20037, USA. achiaram@gwu.edu.
authors.forename: Anne
authors.initials: A
authors.lastname: Chiaramello
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004265:DNA Helicases / Q000032:analysis* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D018386:Kinetochores / Q000201:enzymology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008938:Mitosis; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D016415:Sequence Alignment; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D004265:DNA Helicases
keywords: Chromosomal segregation; Hexameric DNA helicases; Kinetochore complex; Mitochondria; Mitosis; Twinkle