Division of Life Science, Center for Cancer Research, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
Division of Life Science, Center for Cancer Research, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
Mutat Res. 2020 May-Dec;821:111716. doi: 10.1016/j.mrfmmm.2020.111716. Epub 2020 Jul 23.
It is well established that Aurora kinases perform critical functions during mitosis. It has become increasingly clear that the Aurora kinases also perform a myriad of non-mitotic functions including DNA damage response. The available evidence indicates that inhibition Aurora kinase A (AURKA) may contribute to the G DNA damage checkpoint through AURKA's functions in PLK1 and CDC25B activation. Both AURKA and Aurora kinase B (AURKB) are also essential in mitotic DNA damage response that guard against DNA damage-induced chromosome segregation errors, including the control of abscission checkpoint and prevention of micronuclei formation. Dysregulation of Aurora kinases can trigger DNA damage in mitosis that is sensed in the subsequent G by a p53-dependent postmitotic checkpoint. Aurora kinases are themselves linked to the G DNA damage checkpoint through p53 and p73 pathways. Finally, several lines of evidence provide a connection between Aurora kinases and DNA repair and apoptotic pathways. Although more studies are required to provide a comprehensive picture of how cells respond to DNA damage, these findings indicate that both AURKA and AURKB are inextricably linked to pathways guarding against DNA damage. They also provide a rationale to support more detailed studies on the synergism between small-molecule inhibitors against Aurora kinases and DNA-damaging agents in cancer therapies.
已经明确的是，极光激酶在有丝分裂过程中发挥着关键作用。越来越明显的是，极光激酶还具有许多非有丝分裂功能，包括 DNA 损伤反应。现有证据表明，抑制 Aurora 激酶 A（AURKA）可能通过 AURKA 在 PLK1 和 CDC25B 激活中的作用，有助于 G1 DNA 损伤检查点。AURKA 和 Aurora 激酶 B（AURKB）在有丝分裂 DNA 损伤反应中也是必不可少的，它们可以防止 DNA 损伤诱导的染色体分离错误，包括对分裂期检查点的控制和预防微核形成。极光激酶的失调会触发有丝分裂中的 DNA 损伤，随后在 G1 期通过 p53 依赖性有丝分裂后检查点来感知这种损伤。极光激酶本身通过 p53 和 p73 途径与 G1 DNA 损伤检查点联系在一起。最后，有几条证据表明极光激酶与 DNA 修复和凋亡途径之间存在联系。尽管还需要更多的研究来提供一幅全面的图景，说明细胞如何对 DNA 损伤做出反应，但这些发现表明，AURKA 和 AURKB 都与防止 DNA 损伤的途径紧密相连。它们还为支持更详细的研究提供了依据，这些研究涉及针对 Aurora 激酶的小分子抑制剂与癌症治疗中 DNA 损伤剂之间的协同作用。
