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多多益善:同型寡聚化如何改变核苷酸还原酶的互作组和功能。

The more the merrier: how homo-oligomerization alters the interactome and function of ribonucleotide reductase.

机构信息

Beverley, East Riding of Yorkshire, HU17 8QH, UK.

Swiss Federal Institute of Technology Lausanne (EPFL), Institute of Chemical Sciences and Engineering, 1015, Lausanne, Switzerland.

出版信息

Curr Opin Chem Biol. 2020 Feb;54:10-18. doi: 10.1016/j.cbpa.2019.09.003. Epub 2019 Nov 15.

Abstract

Stereotyped as a nexus of dNTP synthesis, the dual-subunit enzyme - ribonucleotide reductase (RNR) - is coming into view as a paradigm of oligomerization and moonlighting behavior. In the present issue of 'omics', we discuss what makes the larger subunit of this enzyme (RNR-α) so interesting, highlighting its emerging cellular interactome based on its unique oligomeric dynamism that dictates its compartment-specific occupations. Linking the history of the field with the multivariable nature of this exceedingly sophisticated enzyme, we further discuss implications of new data pertaining to DNA-damage response, S-phase checkpoints, and ultimately tumor suppression. We hereby hope to provide ideas for those interested in these fields and exemplify conceptual frameworks and tools that are useful to study RNR's broader roles in biology.

摘要

刻板地认为是 dNTP 合成的枢纽,双亚基酶 - 核糖核苷酸还原酶(RNR)- 正在成为聚合和兼职行为的典范。在本期的“组学”中,我们讨论了是什么使得这种酶的大亚基(RNR-α)如此有趣,强调了基于其独特的寡聚动力学的新兴细胞相互作用组,这种动力学决定了其特定隔室的占据。我们将该领域的历史与这种极其复杂的酶的多变量性质联系起来,进一步讨论了与 DNA 损伤反应、S 期检查点以及最终肿瘤抑制相关的新数据的意义。我们希望为对这些领域感兴趣的人提供思路,并举例说明有用的概念框架和工具,以研究 RNR 在生物学中的更广泛作用。

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