Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons

doi:10.1126/science.abb9032

GSTDTAP > 气候变化

DOI	10.1126/science.abb9032
	Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons
	Dylan A. Reid; Patrick J. Reed; Johannes C. M. Schlachetzki; Ioana I. Nitulescu; Grace Chou; Enoch C. Tsui; Jeffrey R. Jones; Sahaana Chandran; Ake T. Lu; Claire A. McClain; Jean H. Ooi; Tzu-Wen Wang; Addison J. Lana; Sara B. Linker; Anthony S. Ricciardulli; Shong Lau; Simon T. Schafer; Steve Horvath; Jesse R. Dixon; Nasun Hah; Christopher K. Glass; Fred H. Gage
	2021-04-02
发表期刊	Science
出版年	2021
英文摘要	Humans have only a limited capacity to generate new neurons. These cells thus need to repair errors in the genome. To better understand this process, Reid et al. developed Repair-seq, a method to locate DNA repair within the genome of stem cell–derived neurons. DNA repair hotspots (DRHs) were more likely to occur within specific genomic features such as gene bodies as well as in genomic formations, open chromatin, and active regulatory regions. This method showed that repair was enriched at sites involved in neuronal function and identity. Furthermore, proteomic data indicated that genes in DRHs are enriched in Alzheimer's disease and that DRHs are more active in aging. These observations link neuronal DNA repair to aging and neurodegeneration. Science , this issue p. [91][1] 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. [1]: /lookup/doi/10.1126/science.abb9032
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/321143
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Dylan A. Reid,Patrick J. Reed,Johannes C. M. Schlachetzki,et al. Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons[J]. Science,2021.
APA	Dylan A. Reid.,Patrick J. Reed.,Johannes C. M. Schlachetzki.,Ioana I. Nitulescu.,Grace Chou.,...&Fred H. Gage.(2021).Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons.Science.
MLA	Dylan A. Reid,et al."Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons".Science (2021).