Danska J S, Guidos C J
Hospital for Sick Children Research Institute, Toronto, ON, Canada.
Semin Immunol. 1997 Jun;9(3):199-206. doi: 10.1006/smim.1997.0072.
V(D)J recombination generates a diverse array of antigen-binding specificities, but breakage and re-joining of DNA segments have grave implications for the maintenance of genomic stability and oncogenic risk. Exposure of eukaryotic cells to genotoxic agents activates a DNA damage checkpoint that induces cell-cycle arrest and DNA repair, or apoptosis. We discuss several lines of evidence implicating DNA-dependent protein kinase (DNA-PK), and the gene mutated in ataxia telangiectasia (ATM), two mammalian homologues of yeast DNA damage-checkpoint genes, in regulating the response to intrinsic DNA damage that occurs during V(D)J recombination.
V(D)J重排产生了一系列多样的抗原结合特异性，但DNA片段的断裂和重新连接对基因组稳定性的维持和致癌风险有着严重影响。真核细胞暴露于基因毒性剂会激活DNA损伤检查点，该检查点会诱导细胞周期停滞、DNA修复或凋亡。我们讨论了几条证据，这些证据表明DNA依赖性蛋白激酶（DNA-PK）以及共济失调毛细血管扩张症（ATM）中发生突变的基因（酵母DNA损伤检查点基因的两个哺乳动物同源物）在调节对V(D)J重排过程中发生的内源性DNA损伤的反应中发挥作用。
