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在类别转换重组过程中修复DNA断裂。

Fixing DNA breaks during class switch recombination.

作者信息

Jolly Christopher J, Cook Adam J L, Manis John P

机构信息

Centenary Institute, The University of Sydney, Sydney, NSW 2006, Australia.

出版信息

J Exp Med. 2008 Mar 17;205(3):509-13. doi: 10.1084/jem.20080356. Epub 2008 Mar 10.

DOI:10.1084/jem.20080356
PMID:18332183
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2275374/
Abstract

Immunoglobulin (Ig) class switch recombination (CSR) involves the breakage and subsequent repair of two DNA sequences, known as switch (S) regions, which flank IgH constant region exons. The resolution of CSR-associated breaks is thought to require the nonhomologous end-joining (NHEJ) DNA repair pathway, but the role of the NHEJ factor DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in this process has been unclear. A new study, in which broken IgH-containing chromosomes in switching B cells were visualized directly, clearly demonstrated that DNA-PKcs and, unexpectedly, the nuclease Artemis are involved in the resolution of switch breaks.

摘要

免疫球蛋白(Ig)类别转换重组(CSR)涉及两个DNA序列(称为转换(S)区域)的断裂及随后的修复,这两个区域位于IgH恒定区外显子两侧。CSR相关断裂的修复被认为需要非同源末端连接(NHEJ)DNA修复途径,但NHEJ因子DNA依赖性蛋白激酶催化亚基(DNA-PKcs)在此过程中的作用尚不清楚。一项新研究直接观察了正在进行类别转换的B细胞中含有断裂IgH的染色体,清楚地表明DNA-PKcs以及出乎意料的核酸酶Artemis参与了转换断裂的修复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2b1/2275374/b8bbc8c40b85/jem2050509f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2b1/2275374/b8bbc8c40b85/jem2050509f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2b1/2275374/b8bbc8c40b85/jem2050509f01.jpg

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J Exp Med. 2008 Mar 17;205(3):557-64. doi: 10.1084/jem.20080044. Epub 2008 Mar 3.
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Non-homologous end-joining, a sticky affair.非同源末端连接,一件棘手的事情。
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IgH class switching and translocations use a robust non-classical end-joining pathway.
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VX-984 is a selective inhibitor of non-homologous end joining, with possible preferential activity in transformed cells.VX-984是一种非同源末端连接的选择性抑制剂,在转化细胞中可能具有优先活性。
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