Weinstock David M, Brunet Erika, Jasin Maria
Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Nat Cell Biol. 2007 Aug;9(8):978-81. doi: 10.1038/ncb1624.
Chromosomal translocations in lymphoid tumours can involve antigen-receptor loci undergoing V(D)J recombination. Here, we show that translocations are recovered from the joining of RAG-generated double-strand breaks (DSBs) on one chromosome to an endonuclease-generated DSB on a second chromosome, providing evidence for the participation of non-RAG DSBs in some lymphoid translocations. Surprisingly, translocations are increased in cells deficient for the nonhomologous end-joining (NHEJ) protein Ku70, implicating non-canonical joining pathways in their etiology.
淋巴肿瘤中的染色体易位可涉及经历V(D)J重组的抗原受体基因座。在此,我们表明,易位是通过将一条染色体上RAG产生的双链断裂(DSB)与第二条染色体上核酸内切酶产生的DSB连接而恢复的,这为非RAG DSB参与某些淋巴易位提供了证据。令人惊讶的是,在非同源末端连接(NHEJ)蛋白Ku70缺陷的细胞中易位增加,这表明非经典连接途径在其病因学中起作用。