@article {13142, title = {Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells}, journal = {Proc Natl Acad Sci U S A}, volume = {108}, number = {51}, year = {2011}, note = {

Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20382-7. Epub 2011 Dec 9.

}, month = {Dec 20}, pages = {20382-7}, type = {Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}t}, edition = {2011/12/14}, abstract = {

Long interspersed element-1 (L1) retrotransposons compose approximately 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.

}, isbn = {1091-6490 (Electronic)00}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22159035}, author = {Coufal, N. G. and Garcia-Perez, J. L. and Peng, G. E. and Marchetto, M. C. and Muotri, A. R. and Mu, Y. and Carson, C. T. and Macia, A. and Moran, J. V. and Gage, F. H.} }