不匹配的修复被超变化所采用
M Cascalho1, J Wong, C Steinberg
1Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0670, USA.
Science (New York, N.Y.)
|March 21, 1998
概括
不匹配修复基因Pms2通常会修复DNA错误. 在这项研究中,Pms2缺乏令人惊地增加了突变,这表明不匹配的修复有助于B细胞的体质突变.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 不匹配修复 (MMR) 系统可以纠正DNA复制错误.
- 具有破坏MMR基因的小鼠,如Pms2,通常表现出突变的表型.
- 身体突变 (SHM) 在B细胞发育过程中引入了免疫球蛋白基因的多样性.
研究的目的:
- 研究Pms2不匹配修复基因在体质突变中的作用.
- 为了确定Pms2缺乏是否影响免疫球蛋白位点的突变率.
- 阐明不匹配修复影响B细胞中SHM的机制.
主要方法:
- 带有中断Pms2等位基因的小鼠的世代交叉到一个准单克隆 (QM) 小鼠背景.
- 分析免疫球蛋白重链和羊链位置的体质突变频率.
- 在Pms2同卵性淘汰,异卵性和野生型QM小鼠之间的突变率的比较.
主要成果:
- 与异构体和野生型QM小鼠相比,对破坏的Pms2等位基具有同异构体的小鼠在免疫球蛋白位点表现出较少的体质突变.
- 这一发现与SHM.的背景下预期的突变变体表型相矛盾.
- 不匹配修复似乎促进,而不是抑制,这些位置的体质突变.
结论:
- Pms2不匹配修复基因在体质突变中发挥作用,可能通过修复而不是消除突变.
- 在超可变的B细胞中,不匹配修复可能会将不匹配的基对的纠正指向新合成的链,从而固定突变.
- 这表明一种新的机制,即DNA修复途径可以促进免疫系统中的遗传多样化.
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