RB stabilizes XPC and promotes cellular NER.
RB stabilizes XPC and promotes cellular NER.
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发表时间：
2010-07
影响因子：
2
通讯作者：
Tabitha M. Hardy;M. Kumar;Martin L. Smith
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文献类型：
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作者：
Tabitha M. Hardy;M. Kumar;Martin L. Smith
长期以来，人们一直认为G（1）/S细胞周期检查点通过延迟S期进入为DNA修复提供了时间。p53肿瘤抑制通路通过调节细胞周期蛋白依赖性激酶抑制剂p21（Waf 1/Cip 1）来调节G（1）/S检查点，但p53也调节核苷酸切除DNA修复蛋白XPC。在这里，使用p53-null细胞系，我们表明，额外的机制稳定XPC蛋白和促进核苷酸切除修复（NER）与G（1）/S检查点。至少一种稳定XPC和使XPC不稳定的机制涉及XPC的泛素介导的降解，因为泛素连接酶抑制剂MG-132阻断XPC降解。视网膜母细胞瘤蛋白RB，在其未磷酸化的形式，实际上稳定XPC和促进NER的宿主细胞再活化实验所测量的。这些数据表明，XPC蛋白和XPC介导的NER与G（1）/S检查点紧密相连，即使在缺乏功能性p53的细胞中也是如此。
It has long been thought that the G(1)/S cell cycle checkpoint allows time for DNA repair by delaying S-phase entry. The p53 tumor suppressor pathway regulates the G(1)/S checkpoint by regulating the cyclin-dependent kinase inhibitor p21(Waf1/Cip1), but p53 also regulates the nucleotide excision DNA repair protein XPC. Here, using p53-null cell lines we show that additional mechanisms stabilize XPC protein and promote nucleotide excision repair (NER) in concert with the G(1)/S checkpoint. At least one mechanism to stabilize and destabilize XPC involves ubiquitin-mediated degradation of XPC, as the ubiquitin ligase inhibitor MG-132 blocked XPC degradation. The retinoblastoma protein RB, in its unphosphorylated form actually stabilized XPC and promoted NER as measured by host cell reactivation experiments. The data suggest that XPC protein and XPC-mediated NER are tightly linked to the G(1)/S checkpoint, even in cells lacking functional p53.