title: Identification of telomere dysfunction in Friedreich ataxia.
abstract: BACKGROUND
  Friedreich ataxia (FRDA) is a progressive inherited neurodegenerative disorder caused by mutation of the FXN gene, resulting in decreased frataxin expression, mitochondrial dysfunction and oxidative stress. A recent study has identified shorter telomeres in FRDA patient leukocytes as a possible disease biomarker.
  
  
  RESULTS
  Here we aimed to investigate both telomere structure and function in FRDA cells. Our results confirmed telomere shortening in FRDA patient leukocytes and identified similar telomere shortening in FRDA patient autopsy cerebellar tissues. However, FRDA fibroblasts showed significantly longer telomeres at early passage, occurring in the absence of telomerase activity, but with activation of an alternative lengthening of telomeres (ALT)-like mechanism. These cells also showed accelerated telomere shortening as population doubling increases. Furthermore, telomere dysfunction-induced foci (TIF) analysis revealed that FRDA fibroblasts have dysfunctional telomeres.
  
  
  CONCLUSIONS
  Our finding of dysfunctional telomeres in FRDA cells provides further insight into FRDA molecular disease mechanisms, which may have implications for future FRDA therapy.
authors.affiliation: Division of Biosciences, Department of Life Sciences, College of Health & Life Sciences, Brunel University London, Uxbridge, UB8 3PH, UK. Sara.Anjomani-Virmouni@brunel.ac.uk.|Synthetic Biology Theme, Institute of Environment, Health & Societies, Brunel University London, Uxbridge, UK. Sara.Anjomani-Virmouni@brunel.ac.uk.
authors.forename: Sara
authors.initials: S
authors.lastname: Anjomani Virmouni
authors.affiliation: Division of Biosciences, Department of Life Sciences, College of Health & Life Sciences, Brunel University London, Uxbridge, UB8 3PH, UK. Sahar.Al-Mahdawi@brunel.ac.uk.|Synthetic Biology Theme, Institute of Environment, Health & Societies, Brunel University London, Uxbridge, UK. Sahar.Al-Mahdawi@brunel.ac.uk.
authors.forename: Sahar
authors.initials: S
authors.lastname: Al-Mahdawi
authors.affiliation: Division of Biosciences, Department of Life Sciences, College of Health & Life Sciences, Brunel University London, Uxbridge, UB8 3PH, UK. Chiranjeevi.Sandi@cruk.cam.ac.uk.|Current address: Uro-Oncology Research Group, Cancer Research UK-Cambridge Institute, University of Cambridge, Cambridge, UK. Chiranjeevi.Sandi@cruk.cam.ac.uk.
authors.forename: Chiranjeevi
authors.initials: C
authors.lastname: Sandi
authors.affiliation: Division of Biosciences, Department of Life Sciences, College of Health & Life Sciences, Brunel University London, Uxbridge, UB8 3PH, UK. Hemad.Yasaei@brunel.ac.uk.
authors.forename: Hemad
authors.initials: H
authors.lastname: Yasaei
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, UK. p.giunti@ucl.ac.uk.
authors.forename: Paola
authors.initials: P
authors.lastname: Giunti
authors.affiliation: Division of Biosciences, Department of Life Sciences, College of Health & Life Sciences, Brunel University London, Uxbridge, UB8 3PH, UK. Predrag.Slijepcevic@brunel.ac.uk.
authors.forename: Predrag
authors.initials: P
authors.lastname: Slijepcevic
authors.affiliation: Division of Biosciences, Department of Life Sciences, College of Health & Life Sciences, Brunel University London, Uxbridge, UB8 3PH, UK. mark.pook@brunel.ac.uk.|Synthetic Biology Theme, Institute of Environment, Health & Societies, Brunel University London, Uxbridge, UK. mark.pook@brunel.ac.uk.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Pook
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D002531:Cerebellum / Q000648:ultrastructure; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D005347:Fibroblasts / Q000648:ultrastructure; D005621:Friedreich Ataxia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007962:Leukocytes / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018384:Oxidative Stress; D011995:Recombination, Genetic; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000648:ultrastructure; D059505:Telomere Homeostasis / Q000502:physiology; D059506:Telomere Shortening / Q000235:genetics; D055815:Young Adult
chemical_list: D019098:Telomerase