PCNA 泛素化/去泛素化的动态调控。
Dynamic regulation of PCNA ubiquitylation/deubiquitylation.
机构信息
Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
FEBS Lett. 2011 Sep 16;585(18):2780-5. doi: 10.1016/j.febslet.2011.05.053. Epub 2011 Jun 1.
Abstract
Proliferating Cell Nuclear Antigen (PCNA) ubiquitylation plays a crucial role in maintaining genomic stability during DNA replication. DNA damage stalling the DNA replication fork induces PCNA ubiquitylation that activates DNA damage bypass to prevent the collapse of DNA replication forks that could potentially produce double-strand breaks and chromosomal rearrangements. PCNA ubiquitylation dictates the mode of bypass depending on the level of ubiquitylation; monoubiquitylation and polyubiquitylation activate error-prone translesion synthesis and error-free template switching, respectively. Due to the error-prone nature of DNA damage bypass, PCNA ubiquitylation needs to be tightly regulated. Here, we review the molecular mechanisms to remove ubiquitin from PCNA including the emerging role of USP1 and ELG1 in this fascinating process.
摘要
增殖细胞核抗原（PCNA）泛素化在 DNA 复制过程中维持基因组稳定性方面起着至关重要的作用。DNA 损伤会使 DNA 复制叉停滞，从而诱导 PCNA 泛素化，激活 DNA 损伤绕过，以防止 DNA 复制叉崩溃，否则可能会产生双链断裂和染色体重排。PCNA 泛素化决定了绕过的模式，具体取决于泛素化的水平；单泛素化和多泛素化分别激活易错跨损伤合成和无差错模板转换。由于 DNA 损伤绕过具有易错性，因此需要严格调控 PCNA 泛素化。在这里，我们综述了从 PCNA 上去除泛素的分子机制，包括 USP1 和 ELG1 在这个迷人过程中的新兴作用。
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