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Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells

Research output: Contribution to journalArticle

  • Nicole G Coufal
  • Josè Luis Garcia-Perez
  • Grace E Peng
  • Maria C N Marchetto
  • Alysson R Muotri
  • Yangling Mu
  • Christian T Carson
  • Angela Macia
  • John V Moran
  • Fred H Gage

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)20382-7
Number of pages6
JournalProceedings of the National Academy of Sciences
Issue number51
Publication statusPublished - 20 Dec 2011


Long interspersed element-1 (L1) retrotransposons compose ∼20% of the mammalian genome, and ongoing L1 retrotransposition events can impact genetic diversity by various mechanisms. Previous studies have demonstrated that endogenous L1 retrotransposition can occur in the germ line and during early embryonic development. In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients. Here, we demonstrate an increase in the retrotransposition efficiency of engineered human L1s in cells that lack or contain severely reduced levels of ataxia telangiectasia mutated, a serine/threonine kinase involved in DNA damage signaling and neurodegenerative disease. We demonstrate that the increase in L1 retrotransposition in ataxia telangiectasia mutated-deficient cells most likely occurs by conventional target-site primed reverse transcription and generate either longer, or perhaps more, L1 retrotransposition events per cell. Finally, we provide evidence suggesting an increase in human-specific L1 DNA copy number in postmortem brain tissue derived from ataxia telangiectasia patients compared with healthy controls. Together, these data suggest that cellular proteins involved in the DNA damage response may modulate L1 retrotransposition.

    Research areas

  • Animals, Ataxia Telangiectasia Mutated Proteins, Cell Cycle Proteins, Cell Line, DNA Repair, DNA-Binding Proteins, Endonucleases, Fibroblasts, Green Fluorescent Proteins, Humans, Long Interspersed Nucleotide Elements, Mice, Mice, Transgenic, Neural Stem Cells, Protein-Serine-Threonine Kinases, Retroelements, Signal Transduction, Tumor Suppressor Proteins

ID: 25156311