DNA ligase I is not essential for mammalian cell viability.
DNA ligase I is not essential for mammalian cell viability.
复制标题
DOI：
10.1016/j.celrep.2014.03.024
复制
发表时间：
2014-04-24
期刊：
影响因子：
8.8
通讯作者：
Yu K
中科院分区：
文献类型：
--
作者：
Han L;Masani S;Hsieh CL;Yu K
在所有脊椎动物中存在的三种 DNA 连接酶中，DNA 连接酶 I (Lig1) 被认为对于 DNA 复制过程中连接冈崎片段至关重要，因此对于细胞活力至关重要。在这里，我们报告了一个惊人的发现，即 Lig1 缺失的鼠 B 细胞系是可行的。令人惊讶的是，Lig1缺失细胞表现出正常的增殖和正常的免疫球蛋白重链类别转换重组，并且对多种DNA损伤剂不过敏。这些发现表明，Lig1 并不是细胞 DNA 复制和修复所必需的，Lig3 或 Lig4 都可以替代 Lig1 在连接冈崎片段中的作用。 Lig1缺失细胞系的建立将极大地促进哺乳动物细胞中DNA连接酶功能的表征，但这一发现本身就深刻地重新确定了连接酶I在DNA复制、修复和重组中的作用。
Of the three DNA ligases present in all vertebrates, DNA ligase I (Lig1) has been considered essential for ligating Okazaki fragments during DNA replication and thereby essential for cell viability. Here, we report the striking finding that a Lig1-null murine B cell line is viable. Surprisingly, the Lig1-null cells exhibit normal proliferation and normal immunoglobulin heavy chain class switch recombination and are not hypersensitive to a wide variety of DNA damaging agents. These findings demonstrate that Lig1 is not absolutely required for cellular DNA replication and repair and that either Lig3 or Lig4 can substitute for the role of Lig1 in joining Okazaki fragments. The establishment of a Lig1-null cell line will greatly facilitate the characterization of DNA ligase function in mammalian cells, but the finding alone profoundly reprioritizes the role of ligase I in DNA replication, repair, and recombination.