在缺乏DNA结合酶IV的小鼠中,晚期胚胎死亡率和受损的V(D) J重组
K M Frank1, J M Sekiguchi, K J Seidl
1The Children's Hospital, Department of Genetics, Harvard University Medical School, Boston, Massachusetts 02115, USA.
Nature
|November 21, 1998
概括
基因链酶IV对V(D) J重组和DNA修复至关重要. 它在小鼠中的无活化会导致胚胎致死性和阻塞的淋巴发育,突出显示其在Ku-依赖性通路之外的关键作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 免疫学 免疫学 免疫学
背景情况:
- DNA双链断裂修复和V(D) J重组利用共同的蛋白质因子.
- 包括Ku70-Ku80和XRCC4在内的DNA-依赖蛋白激酶 (DNA-PK) 组件都参与其中.
- XRCC4的确切功能以及哺乳动物DNA连接酶,特别是DNA连接酶IV的体内作用仍然不清楚.
研究的目的:
- 为了研究DNA结合酶IV的体内功能.
- 在哺乳动物模型中确定DNA联酶IV缺乏的后果.
主要方法:
- 在小鼠中DNA联酶IV的基因失活.
- 对胚胎致死率,淋巴发育和V(D) J重组的分析.
- 酶IV缺乏胚胎纤维细胞的表型特征,包括对电离辐射的敏感性,生长和衰老.
主要成果:
- 在小鼠中,DNA联酶IV基因的失活导致了晚期胚胎致死性.
- 在Ligase IV缺乏的小鼠中,淋巴结合被阻断,V(D) J结合被废除.
- 缺乏联酶IV的纤维细胞对电离辐射,生长缺陷和过早衰老具有敏感性,类似于缺乏Ku的细胞.
结论:
- 基因链酶IV对于V(D) J重组是不可或缺的,并且可能在DNA修复中发挥关键作用.
- 观察到的表型表明DNA末端连接过程受损,涉及Ku子单元和DNA联酶IV.
- 基因联结酶IV具有独立于Ku的生命力和淋巴发育必不可少的功能,这表明它在细胞过程中的更广泛作用.
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