CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome
CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome
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DOI：
10.1101/gad.378206
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发表时间：
2006-06-01
影响因子：
10.5
通讯作者：
Nakatani, Yoshihiro
中科院分区：
文献类型：
--
作者：
Groisman, Regina;Kuraoka, Isao;Nakatani, Yoshihiro
CSA或CSB互补基因的突变会导致柯凯因综合征，这是一种严重的遗传疾病，会导致患者在成年早期死亡。CSA和CSB在转录偶联修复（TCR）途径中起作用，但它们的功能关系尚不清楚。我们之前已经表明，CSA是E3泛素连接酶复合物的一个亚基。在这里，我们证明CSB是这种连接酶的底物：在紫外线照射下，CSB在修复过程的后期以蛋白酶体和csa依赖的方式降解。此外，我们证明了CSB降解对tcr后转录恢复和Cockayne综合征的重要性。我们的研究结果首次揭示了CSA和CSB之间的功能关系。
Mutations in the CSA or CSB complementation genes cause the Cockayne syndrome, a severe genetic disorder that results in patients' death in early adulthood. CSA and CSB act in a transcription-coupled repair (TCR) pathway, but their functional relationship is not understood. We have previously shown that CSA is a subunit of an E3 ubiquitin ligase complex. Here we demonstrate that CSB is a substrate of this ligase: Following UV irradiation, CSB is degraded at a late stage of the repair process in a proteasome- and CSA-dependent manner. Moreover, we demonstrate the importance of CSB degradation for post-TCR recovery of transcription and for the Cockayne syndrome. Our results unravel for the first time the functional relationship between CSA and CSB.