Healing the wounds inflicted by Sleeping Beauty transposition by double-strand break repair in mammalian somatic cells
Healing the wounds inflicted by Sleeping Beauty transposition by double-strand break repair in mammalian somatic cells
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DOI：
10.1016/s1097-2765(03)00524-0
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发表时间：
2004-01-30
期刊：
影响因子：
16
通讯作者：
Ivics, Z
中科院分区：
文献类型：
--
作者：
Izsvák, Z;Stüwe, EE;Ivics, Z
睡美人 (SB) 元件是探测脊椎动物转座子与宿主相互作用的有用工具。我们研究了哺乳动物细胞中 SB 转座对 DNA 修复因子的需求。非同源末端连接 (NHEJ) 因子，包括 Ku、DNA-PKcs 和 Xrcc4 以及 Xrcc3/Rad51C（一种在同源重组过程中发挥作用的复合物）是有效转座所必需的。 NHEJ 在体细胞转座子切除位点的修复中起主导作用。 Artemis 对于转座来说是可有可无的，这与切除部位缺乏发夹结构一致。 Ku 与 SB 转座酶发生物理相互作用。 DNA-PKcs 是转座的限制因素，除了修复之外，还具有独立于其激酶活性的转座功能。 ATM 参与切除部位修复并影响转位率。修复因子在转座和 V(D)J 重组中的重叠但不同的作用可能会影响这些机械上相似过程的结果。
The Sleeping Beauty (SB) element is a useful tool to probe transposon-host interactions in vertebrates. We investigated requirements of DNA repair factors for SB transposition in mammalian cells. Factors of non-homologous end joining (NHEJ), including Ku, DNA-PKcs, and Xrcc4 as well as Xrcc3/Rad51C, a complex that functions during homologous recombination, are required for efficient transposition. NHEJ plays a dominant role in repair of transposon excision sites in somatic cells. Artemis is dispensable for transposition, consistent with the lack of a hairpin structure at excision sites. Ku physically interacts with the SB transposase. DNA-PKcs is a limiting factor for transposition and, in addition to repair, has a function in transposition that is independent from its kinase activity. ATM is involved in excision site repair and affects transposition rates. The overlapping but distinct roles of repair factors in transposition and in V(D)J recombination might influence the outcomes of these mechanistically similar processes.