长神经基因在神经干细胞/原始细胞中存在反复发生的DNA断裂集群
Pei-Chi Wei1, Amelia N Chang1, Jennifer Kao1
1Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Cell
|February 13, 2016
概括
DNA双链断裂对于神经发展至关重要. 这项研究确定了神经干细胞中具有复发性DSB的特定基因组区域,揭示了与神经功能和疾病相关的脆弱区域.
科学领域:
- 基因组学
- 神经科学
- 分子生物学
背景情况:
- 不同类末端连接 (NHEJ) 修复DNA双链断裂 (DSB) 对神经发育至关重要.
- 大脑细胞的体内基因组变异可能涉及DSB中间体.
研究的目的:
- 在初级神经干细胞/原生细胞 (NSPC) 中识别具有复发性DSB的基因组区域,采用无偏见的高通量方法.
- 描述这些DSB站点的基因组特征和功能影响.
主要方法:
- 采用一个公正的高通量方法来检测NSPC中的反复发生的DSB集群 (RDC).
- 使用阿菲迪科林诱导轻微的复制压力来揭示脆弱的部位.
- 对基因体,复制时间和基因功能的RDC位置进行分析.
主要成果:
- 确定了27个复发的DSB集群 (RDC),所有这些都位于基因体内.
- 大多数NSPCRDC在复制压力下被检测出来,突出显示复制相关的脆弱部位.
- 主要发生在长,转录,晚复制的基因中.
- 几乎90%的RDC含有的基因参与突触功能和/或神经细胞粘附.
- 这些基因的很大一部分也与瘤抑制和/或精神障碍有关.
结论:
- 对NSPCRDC的表征提供了关于神经细胞基因脆弱性的见解.
- DNA 断裂可能会影响神经发育和神经功能,并可能与神经和精神疾病有关.
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