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In: Genome Editing in Neurosciences [Internet]. Cham (CH): Springer; 2017.
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Affiliations
Affiliations
1 Howard Hughes Medical Institute, Boston, MA, USA
2 Program in Cellular and Molecular Medicine, Boston Children’s Hospital, 02115, Boston, MA, USA
3 Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA
4 Department of Neurological Surgery and Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94158, USA
Book Affiliations
1 Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
2 Department of Brain and Cognitive Science, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
3 Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California, USA
1 Howard Hughes Medical Institute, Boston, MA, USA
2 Program in Cellular and Molecular Medicine, Boston Children’s Hospital, 02115, Boston, MA, USA
3 Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA
4 Department of Neurological Surgery and Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94158, USA
Book Affiliations
1 Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
2 Department of Brain and Cognitive Science, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
3 Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California, USA
The repair of mammalian DNA double-strand breaks (DSBs) by classical non-homologous end joining (C-NHEJ) suppresses genomic instability and cancer and is required for development of the immune and nervous system. We hypothesize that proper repair of neural DSBs via C-NHEJ or other end-joining pathways is critical for neural functionality and homeostasis over time and that improper DSB repair could contribute to complex psychiatric and neurodegenerative diseases. Here, we summarize various findings made by our laboratory and others over the years that support this hypothesis. This evidence includes, most recently, our discovery of a set of genes, of which most serve neural functions, that can serve as targets of recurrent DSBs in primary neural stem and progenitor cells. We also present a speculative model, based on our findings, of mechanisms by which recurrent DSBs in neural genes can generate neuronal diversity and contribute to neuropsychiatric disease.
Alt FW, Baltimore D (1982) Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions. Proc Natl Acad Sci USA 79:4118–4122
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Ferguson DO, Alt FW (2001) DNA double strand break repair and chromosomal translocation: lessons from animal models. Oncogene 20:5572–5579
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