DNA-dependent protein kinase activity is not required for immunoglobulin class switching.
DNA-dependent protein kinase activity is not required for immunoglobulin class switching.
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DOI：
10.1084/jem.20001871
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发表时间：
2002-12-02
期刊：
影响因子：
--
通讯作者：
Bosma MJ
中科院分区：
文献类型：
--
作者：
Bosma GC;Kim J;Urich T;Fath DM;Cotticelli MG;Ruetsch NR;Radic MZ;Bosma MJ
类转换重组（CSR），类似于V（D）J重组，被认为涉及DNA双链断裂和修复的非同源末端连接途径。该途径的关键组分是DNA依赖性蛋白激酶（DNA-PK），其由催化亚基（DNA-PKcs）和DNA结合异二聚体（Ku 70/80）组成。为了测试DNA-PKcs活性是否是CSR所必需的，我们检测了来自具有定点H和L链转基因的scid小鼠的IgM+ B细胞是否能够经历CSR。尽管这些小鼠的B细胞显示缺乏DNA-PKcs活性，但它们能够以与对照转基因和非转基因scid/+小鼠（scid突变杂合子）的B细胞接近的效率从IgM转换为IgG或伊加。我们的结论是，CSR，不像V（D）J重组，可以很容易地发生在DNA-PKcs活性的情况下。我们建议非同源末端连接可能不是（主要或唯一）的机制，用于修复CSR过程中的DNA断裂。
Class switch recombination (CSR), similar to V(D)J recombination, is thought to involve DNA double strand breaks and repair by the nonhomologous end–joining pathway. A key component of this pathway is DNA-dependent protein kinase (DNA-PK), consisting of a catalytic subunit (DNA-PKcs) and a DNA-binding heterodimer (Ku70/80). To test whether DNA-PKcs activity is essential for CSR, we examined whether IgM+ B cells from scid mice with site-directed H and L chain transgenes were able to undergo CSR. Although B cells from these mice were shown to lack DNA-PKcs activity, they were able to switch from IgM to IgG or IgA with close to the same efficiency as B cells from control transgenic and nontransgenic scid/+ mice, heterozygous for the scid mutation. We conclude that CSR, unlike V(D)J recombination, can readily occur in the absence of DNA-PKcs activity. We suggest nonhomologous end joining may not be the (primary or only) mechanism used to repair DNA breaks during CSR.
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影响因子：
4.4
作者：
CHEN, JZ;TROUNSTINE, M;HUSZAR, D
通讯作者：
HUSZAR, D
影响因子：
64.8
作者：
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影响因子：
15.3
作者：
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DOI：
10.1073/pnas.95.26.15559
发表时间：
1998-12-22
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
32.4
作者：
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通讯作者：
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