Laboratory of Chromosome Biology and Genomic Stability, Department of Molecular and Experimental Medicine, The Scripps Research Institute La Jolla, CA, USA.
Front Genet. 2013 Jul 9;4:128. doi: 10.3389/fgene.2013.00128. eCollection 2013.
RING (Really Interesting New Gene) domain-containing E3 ubiquitin ligases comprise a large family of enzymes that in combination with an E2 ubiquitin-conjugating enzyme, modify target proteins by attaching ubiquitin moieties. A number of RING E3s play an essential role in the cellular response to DNA damage highlighting a crucial contribution for ubiquitin-mediated signaling to the genome surveillance pathway. Among the RING E3s, RNF8 and RNF168 play a critical role in the response to double stranded breaks, one of the most deleterious types of DNA damage. These proteins act as positive regulators of the signaling cascade that initiates at DNA lesions. Inactivation of these enzymes is sufficient to severely impair the ability of cells to respond to DNA damage. Given their central role in the pathway, several layers of regulation act at this nodal signaling point. Here we will summarize current knowledge on the roles of RNF8 and RNF168 in maintaining genome integrity with particular emphasis on recent insights into the multiple layers of regulation that act on these enzymes to fine-tune the cellular response to DNA lesions.
RING（真有趣的新基因）结构域包含的 E3 泛素连接酶组成了一个庞大的酶家族，它们与 E2 泛素缀合酶结合，通过附着泛素分子来修饰靶蛋白。许多 RING E3 在细胞对 DNA 损伤的反应中起着至关重要的作用，这突显了泛素介导的信号对基因组监测途径的重要贡献。在 RING E3 中，RNF8 和 RNF168 在双链断裂的反应中起着关键作用，双链断裂是最具破坏性的 DNA 损伤类型之一。这些蛋白质作为信号级联反应的正调节剂，在 DNA 损伤处起始。这些酶的失活足以严重损害细胞对 DNA 损伤作出反应的能力。鉴于它们在该途径中的核心作用，在这个节点信号点上有几个调节层发挥作用。在这里，我们将总结 RNF8 和 RNF168 在维持基因组完整性方面的作用，特别强调最近对作用于这些酶的多层次调节的深入了解，以微调细胞对 DNA 损伤的反应。
