A non-catalytic function of Rev1 in translesion DNA synthesis and mutagenesis is mediated by its stable interaction with Rad5
A non-catalytic function of Rev1 in translesion DNA synthesis and mutagenesis is mediated by its stable interaction with Rad5
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DOI：
10.1016/j.dnarep.2012.10.003
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发表时间：
2013-01-01
期刊：
影响因子：
3.8
通讯作者：
Wang, Zhigang
中科院分区：
文献类型：
--
作者：
Kuang, Lisha;Kou, Haiping;Wang, Zhigang
DNA损伤耐受包括模板转换和跨损伤合成，是复制过程中对未修复DNA损伤的主要细胞机制。Rev 1途径构成了模型细胞系统中跨损伤合成和碱基损伤诱导突变的主要机制。Rev 1是一种dCMP转移酶，但另外在跨损伤合成中发挥非催化功能。使用酵母模型系统，我们试图进一步了解Rev 1的非催化功能。Rev 1通过Rev 1的C-末端区域和Rad 5的N-末端区域与Rad 5（模板转换途径的中心组分）稳定地相互作用。支持这种相互作用的功能意义，Rev 1途径和Rad 5都需要translesion合成和1，N-6-乙烯基腺嘌呤的诱变。此外，通过突变Rev 1破坏Rev 1 Rad 5相互作用并不影响其dCMP转移酶，但导致Rev 1在UV诱导的DNA损伤的translesion合成中的非催化功能失活。缺失分析表明，Rev 1的C-末端21个氨基酸序列是其与Rad 5相互作用所必需的，并且是其非催化功能所必需的。缺失分析还涉及Rev 1的C-末端区域在其负调控。这些结果表明，一个非催化功能的Rev 1在translesion合成和诱变介导的与Rad 5的相互作用。(C)2012 Elsevier B. V.保留所有权利。
DNA damage tolerance consisting of template switching and translesion synthesis is a major cellular mechanism in response to unrepaired DNA lesions during replication. The Rev1 pathway constitutes the major mechanism of translesion synthesis and base damage-induced mutagenesis in model cell systems. Rev1 is a dCMP transferase, but additionally plays non-catalytic functions in translesion synthesis. Using the yeast model system, we attempted to gain further insights into the non-catalytic functions of Rev1. Rev1 stably interacts with Rad5 (a central component of the template switching pathway) via the C-terminal region of Rev1 and the N-terminal region of Rad5. Supporting functional significance of this interaction, both the Rev1 pathway and Rad5 are required for translesion synthesis and mutagenesis of 1,N-6-ethenoadenine. Furthermore, disrupting the Rev1 Rad5 interaction by mutating Rev1 did not affect its dCMP transferase, but led to inactivation of the Rev1 non-catalytic function in translesion synthesis of UV-induced DNA damage. Deletion analysis revealed that the C-terminal 21-amino acid sequence of Rev1 is uniquely required for its interaction with Rad5 and is essential for its non-catalytic function. Deletion analysis additionally implicated a C-terminal region of Rev1 in its negative regulation. These results show that a non-catalytic function of Rev1 in translesion synthesis and mutagenesis is mediated by its interaction with Rad5. (C) 2012 Elsevier B.V. All rights reserved.