DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes
DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes
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DOI：
10.1016/s1097-2765(00)80147-1
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发表时间：
1998-10-01
期刊：
影响因子：
16
通讯作者：
Lieber, MR
中科院分区：
文献类型：
--
作者：
Grawunder, U;Zimmer, D;Lieber, MR
非同源DNA末端连接（NHEJ）是修复双链DNA断裂的主要途径。V（D）J重组是一种双链DNA断裂和重新连接的过程，其连接步骤依赖于NHEJ。在这里，我们表明，在人类前B细胞系中的两个DNA连接酶IV等位基因的靶向破坏使细胞对电离辐射敏感，并消除V（D）J重组。这种表型只能通过与DNA连接酶IV互补来逆转，而不能通过表达其余两种连接酶（DNA连接酶I或III）中的任一种来逆转。因此，DNA连接酶IV是负责NHEJ和V（D）J重组中的连接步骤的活性。
Nonhomologous DNA end joining (NHEJ) is the major pathway for repairing double-strand DNA breaks. V(D)J recombination is a double-strand DNA breakage and rejoining process that relies on NHEJ for the joining steps. Here we show that the targeted disruption of both DNA ligase IV alleles in a human pre-B cell line renders the cells sensitive to ionizing radiation and ablates V(D)J recombination. This phenotype can only be reversed by complementation with DNA ligase IV but not by expression of either of the remaining two ligases, DNA ligase I or III. Hence, DNA ligase IV is the activity responsible for the ligation step in NHEJ and in V(D)J recombination.