Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation
Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation
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DOI：
10.1038/nature01965
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发表时间：
2003-09-11
期刊：
影响因子：
64.8
通讯作者：
Ulrich, HD
中科院分区：
文献类型：
--
作者：
Stelter, P;Ulrich, HD
通过泛素的蛋白质修饰正在成为真核生物中各种生物过程的信号，包括调节的蛋白质水解，但也用于非降解功能，如蛋白质定位，DNA修复和染色质结构的调节（1-4）。一种小的泛素相关修饰物（SUMO）使用类似的缀合系统，有时会抵消泛素化的影响（5）。泛素和SUMO竞争对增殖细胞核抗原（PCNA）的修饰，PCNA是DNA复制和修复的重要持续合成因子（6）。尽管多泛素化由RAD 6途径的组分介导并促进无错误修复，但SUMO修饰与复制相关（6-9）。在这里，我们表明，RAD 6介导的单泛素化的PCNA激活translesion DNA合成的损伤耐受聚合酶eta和zeta在酵母中。此外，聚合酶zeta的差异影响的单泛素和SUMO修饰的PCNA。泛素化是损伤诱导的突变所必需的，而SUMO和单泛素在没有DNA损伤的情况下都有助于自发突变。我们的研究结果分配功能SUMO在S期，并证明如何泛素和SUMO，通过调节复制和修复的准确性，有助于整体基因组的稳定性。
Protein modification by ubiquitin is emerging as a signal for various biological processes in eukaryotes, including regulated proteolysis, but also for non-degradative functions such as protein localization, DNA repair and regulation of chromatin structure(1-4). A small ubiquitin-related modifier (SUMO) uses a similar conjugation system that sometimes counteracts the effects of ubiquitination(5). Ubiquitin and SUMO compete for modification of proliferating cell nuclear antigen (PCNA), an essential processivity factor for DNA replication and repair(6). Whereas multi-ubiquitination is mediated by components of the RAD6 pathway and promotes error-free repair, SUMO modification is associated with replication(6-9). Here we show that RAD6-mediated mono-ubiquitination of PCNA activates translesion DNA synthesis by the damage-tolerant polymerases eta and zeta in yeast. Moreover, polymerase zeta is differentially affected by mono-ubiquitin and SUMO modification of PCNA. Whereas ubiquitination is required for damage-induced mutagenesis, both SUMO and mono-ubiquitin contribute to spontaneous mutagenesis in the absence of DNA damage. Our findings assign a function to SUMO during S phase and demonstrate how ubiquitin and SUMO, by regulating the accuracy of replication and repair, contribute to overall genomic stability.