Put a RING on it: regulation and inhibition of RNF8 and RNF168 RING finger E3 ligases at DNA damage sites.
Put a RING on it: regulation and inhibition of RNF8 and RNF168 RING finger E3 ligases at DNA damage sites.
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DOI：
10.3389/fgene.2013.00128
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发表时间：
2013
影响因子：
3.7
通讯作者：
Denchi EL
中科院分区：
文献类型：
--
作者：
Bartocci C;Denchi EL
含有E3泛素连接酶的RING（真正有趣的新基因）结构域包括一个大家族的酶，它与E2泛素结合酶结合，通过连接泛素片段来修饰靶蛋白。许多RING E3s在细胞对DNA损伤的反应中起着重要作用，突出了泛素介导的基因组监视途径的信号传导的重要贡献。在RING E3s中，RNF8和RNF168在对双链断裂（最有害的DNA损伤类型之一）的反应中起关键作用。这些蛋白作为信号级联反应的积极调节因子，在DNA损伤处启动。这些酶的失活足以严重损害细胞对DNA损伤的反应能力。考虑到它们在通路中的中心作用，在这个节点信号点上有几层调节作用。在这里，我们将总结目前关于RNF8和RNF168在维持基因组完整性方面的作用的知识，并特别强调最近对作用于这些酶的多层调控的见解，以微调细胞对DNA损伤的反应。
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.