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DOI10.1126/science.abb9032
Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons
Reid D.A.; Reed P.J.; Schlachetzki J.C.M.; Nitulescu I.I.; Chou G.; Tsui E.C.; Jones J.R.; Chandran S.; Lu A.T.; McClain C.A.; Ooi J.H.; Wang T.-W.; Lana A.J.; Linker S.B.; Ricciardulli A.S.; Lau S.; Schafer S.T.; Horvath S.; Dixon J.R.; Hah N.; Glass C.K.; Gage F.H.
发表日期2021
ISSN0036-8075
起始页码91
结束页码94
卷号372期号:6537
英文摘要Neurons are the longest-lived cells in our bodies and lack DNA replication, which makes them reliant on a limited repertoire of DNA repair mechanisms to maintain genome fidelity. These repair mechanisms decline with age, but we have limited knowledge of how genome instability emerges and what strategies neurons and other long-lived cells may have evolved to protect their genomes over the human life span. A targeted sequencing approach in human embryonic stem cell-induced neurons shows that, in neurons, DNA repair is enriched at well-defined hotspots that protect essential genes. These hotspots are enriched with histone H2A isoforms and RNA binding proteins and are associated with evolutionarily conserved elements of the human genome. These findings provide a basis for understanding genome integrity as it relates to aging and disease in the nervous system. © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
英文关键词nucleoside analog; RNA binding protein; 5-ethynyl-2'-deoxyuridine; deoxyuridine; histone; RNA binding protein; spacer DNA; DNA; genome; nervous system; neurology; protein; aging; Article; binding site; brain disease; chemical structure; DNA repair; gene amplification; gene mapping; genetic association; high throughput sequencing; mitosis; nerve cell; nonhuman; polymerase chain reaction; priority journal; promoter region; RNA binding; cytology; DNA damage; DNA sequence; embryonic stem cell; genetic transcription; genetics; genomic instability; human; human genome; metabolism; mitosis; mutation; nerve cell; neurologic disease; Aging; Deoxyuridine; DNA Damage; DNA Repair; DNA, Intergenic; Embryonic Stem Cells; Genome, Human; Genomic Instability; Histones; Humans; Mitosis; Mutation; Nervous System Diseases; Neurons; Promoter Regions, Genetic; RNA-Binding Proteins; Sequence Analysis, DNA; Transcription, Genetic
语种英语
来源期刊Science
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/245201
作者单位Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, San Diego, CA 92037-1002, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92037-0651, United States; Next Generation Sequencing Core, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, San Diego, CA 92037-1002, United States; Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, San Diego, CA 92037-1002, United States; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, United States; Department of Biostatistics, School of Public Health, University of California, Los Angeles, Los Angeles, CA 90095, United States
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Reid D.A.,Reed P.J.,Schlachetzki J.C.M.,et al. Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons[J],2021,372(6537).
APA Reid D.A..,Reed P.J..,Schlachetzki J.C.M..,Nitulescu I.I..,Chou G..,...&Gage F.H..(2021).Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons.Science,372(6537).
MLA Reid D.A.,et al."Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons".Science 372.6537(2021).
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