研究揭示人类神经元中的基因组修复机制
2021-04-06   阅读:688   来源:科学

美国索尔克生物研究所Fred H. Gage、Dylan A. Reid等研究人员合作揭示人类神经元中的基因组修复机制。该研究于2021年4月2日发表于国际一流学术期刊《科学》。

研究人员通过人类胚胎干细胞诱导神经元的靶向测序方法表明,在神经元中,DNA修复富集在保护必需基因的已知热点。这些热点富含组蛋白H2A亚型和RNA结合蛋白,并与人类基因组的进化保守元件有关。这些发现为理解基因组完整性提供了基础,因为这与神经系统的衰老和疾病有关。 

据介绍,神经元是人体内寿命最长的细胞,并且缺乏DNA复制,这使得其依赖于有限的DNA修复机制来维持基因组的完整性。这些修复机制会随着年龄的增长而下降,但是人们对基因组不稳定性如何出现以及神经元和其他长寿细胞可能进化出什么样的策略来保护其基因组知之甚少。 

附:英文原文

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

Author: 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

Issue&Volume: 2021/04/02

Abstract: 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.

DOI: 10.1126/science.abb9032

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