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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.<\/jats:p>","DOI":"10.1073\/pnas.1100273108","type":"journal-article","created":{"date-parts":[[2011,12,9]],"date-time":"2011-12-09T23:50:48Z","timestamp":1323474648000},"page":"20382-20387","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":231,"title":["Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells"],"prefix":"10.1073","volume":"108","author":[{"given":"Nicole G.","family":"Coufal","sequence":"first","affiliation":[{"name":"Laboratory of Genetics, Salk Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e8 Luis","family":"Garcia-Perez","sequence":"additional","affiliation":[{"name":"Andalusian Stem Cell Bank, Centro de Investigaci\u00f3n Biom\u00e9dica, Consejer\u00eda Salud Junta de Andalucia-Universidad de Granada, 18100 Granada, Spain;"},{"name":"Department of Human DNA Variability, Pfizer-University of Granada and Andalusian Government Center for Genomics and Oncology (GENYO), 18007 Granada, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace E.","family":"Peng","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Salk Institute, La Jolla, CA 92037;"},{"name":"Cardiovascular Research Institute, University of California, San Francisco, CA 94158;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C. 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