Cellular localization of human Rad51C and regulation of ubiquitin-mediated proteolysis of Rad51
Cellular localization of human Rad51C and regulation of ubiquitin-mediated proteolysis of Rad51
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DOI：
10.1002/jcb.20640
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发表时间：
2005-12-15
影响因子：
4
通讯作者：
Knight, KL
中科院分区：
文献类型：
--
作者：
Bennett, BT;Knight, KL
Rad51催化的同源重组是无脊椎动物细胞修复DNA双链断裂和维持基因组完整性的重要途径。被称为 Rad51 旁系同源物的五种蛋白质可促进 Rad51 活性，并被认为在重组途径的各个阶段（在某些情况下为多个阶段）发挥作用。天然 Rad51 的成像研究揭示了其对 DNA 损伤的细胞反应，但旁系同源蛋白的可视化却取得了有限的成功。在这项研究中，我们能够检测人体细胞中的内源性 Rad51C 和 Xrcc3。为了确定 Rad51、Rad51C 和 Xrcc3 在 DNA 损伤和修复过程中如何影响彼此的定位模式，我们意外地观察到 Rad51 通过泛素介导的蛋白酶体途径降解，是重组 DNA 修复的自然部分。此外，我们发现 Rad51C 在调节这一过程中发挥着重要作用。
Rad51-catalyzed homologous recombination is an important pathway for repair of DNA double strand breaks and maintenance of genome integrity invertebrate cells. Five proteins referred to as Rad51 paralogs promote Rad51 activity and are proposed to act at various, and in some cases, Multiple stages in the recombination pathway. Imaging studies of native Rad51 have revealed its cellular response to DNA damage, yet visualization of the paralog proteins has met with limited success. In this study, we are able to detect endogenous Rad51C and Xrcc3 in human cells. In an effort to determine how Rad51, Rad51C, and Xrcc3 influence the pattern of localization of each other over the time course of DNA damage and repair, we have made the unexpected observation that Rad51 degradation via the ubiquitin-mediated proteasome pathway occurs as a natural part of recombinational DNA repair. Additionally, we find that Rad51C plays an important role in regulating this process.