Ubiquitin and Ubiquitin-Like Proteins Are Essential Regulators of DNA Damage Bypass.
Ubiquitin and Ubiquitin-Like Proteins Are Essential Regulators of DNA Damage Bypass.
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泛素和泛素样蛋白是DNA损伤旁路的重要调节因子。
DOI：
10.3390/cancers12102848
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发表时间：
2020-10-02
期刊：
影响因子：
5.2
通讯作者：
Woodgate R
中科院分区：
文献类型：
--
作者：
Wilkinson NA;Mnuskin KS;Ashton NW;Woodgate R
泛素和泛素样蛋白与细胞内的许多其他蛋白质结合，以调节其稳定性，定位和活性。这些修饰对于正常的细胞功能是必不可少的，这些过程的破坏有助于许多癌症类型。在这篇综述中，我们讨论了泛素和泛素样蛋白如何调节DNA损伤旁路的专门复制途径，以及这些过程的破坏如何有助于癌症的发展。我们还讨论了癌细胞的存活如何依赖于DNA损伤旁路，以及如何通过泛素和泛素样蛋白靶向调节这些途径可能是抗癌治疗的有效策略。许多内源性和外源性因素可以以DNA损伤和突变的形式诱导人类细胞中的基因组不稳定性，使其易于发生癌症。正常细胞依赖于DNA损伤旁路途径，如跨损伤合成（TLS）和模板转换（TS）来复制过去的损伤，否则可能导致延长的复制应激和致命的双链断裂（DSB）。然而，由于参与TLS的特异性聚合酶的保真度较低，这些途径的激活和抑制必须通过翻译后修饰（如泛素化）进行严格调控，以限制诱变的风险。许多癌细胞依赖于DNA损伤旁路的失调来促进致癌和肿瘤形成，通常使它们对化疗剂的DNA损伤具有更高的抗性。在这篇综述中，我们讨论了泛素和泛素样蛋白在调节人类细胞DNA损伤旁路中的关键功能，并强调了这些过程在癌症进展中被解除管制的方式，并可能成为癌症治疗的靶点。
Ubiquitin and ubiquitin-like proteins are conjugated to many other proteins within the cell, to regulate their stability, localization, and activity. These modifications are essential for normal cellular function and the disruption of these processes contributes to numerous cancer types. In this review, we discuss how ubiquitin and ubiquitin-like proteins regulate the specialized replication pathways of DNA damage bypass, as well as how the disruption of these processes can contribute to cancer development. We also discuss how cancer cell survival relies on DNA damage bypass, and how targeting the regulation of these pathways by ubiquitin and ubiquitin-like proteins might be an effective strategy in anti-cancer therapies. Many endogenous and exogenous factors can induce genomic instability in human cells, in the form of DNA damage and mutations, that predispose them to cancer development. Normal cells rely on DNA damage bypass pathways such as translesion synthesis (TLS) and template switching (TS) to replicate past lesions that might otherwise result in prolonged replication stress and lethal double-strand breaks (DSBs). However, due to the lower fidelity of the specialized polymerases involved in TLS, the activation and suppression of these pathways must be tightly regulated by post-translational modifications such as ubiquitination in order to limit the risk of mutagenesis. Many cancer cells rely on the deregulation of DNA damage bypass to promote carcinogenesis and tumor formation, often giving them heightened resistance to DNA damage from chemotherapeutic agents. In this review, we discuss the key functions of ubiquitin and ubiquitin-like proteins in regulating DNA damage bypass in human cells, and highlight ways in which these processes are both deregulated in cancer progression and might be targeted in cancer therapy.
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影响因子：
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