Jolly Christopher J, Cook Adam J L, Manis John P
Centenary Institute, The University of Sydney, Sydney, NSW 2006, Australia.
J Exp Med. 2008 Mar 17;205(3):509-13. doi: 10.1084/jem.20080356. Epub 2008 Mar 10.
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.
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。