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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Macia, Angela Carson, Christian T. Garcia-perez, Josè Luis Mu, Yangling Gage, Fred H. Peng, Grace E. Coufal, Nicole G. Muotri, Alysson R. Marchetto, Maria C. N. Moran, John V. |
| Description | Author Affiliation: Coufal NG ( Laboratory of Genetics, Salk Institute, La Jolla, CA 92037, USA.); |
| Abstract | Long interspersed element-1 (L1) retrotransposons compose â ¼20% 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 51 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Cycle Proteins Genetics DNA-Binding Proteins Long Interspersed Nucleotide Elements Neural Stem Cells Cytology Protein-Serine-Threonine Kinases Retroelements Tumor Suppressor Proteins Animals Ataxia Telangiectasia Mutated Proteins Cell Line DNA Repair Endonucleases Metabolism Fibroblasts Green Fluorescent Proteins Mice Mice, Transgenic Signal Transduction Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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