Similarities and differences between Arabidopsis PCNA1 and PCNA2 in complementing the yeast DNA damage tolerance defect

Similarities and differences between Arabidopsis PCNA1 and PCNA2 in complementing the yeast DNA damage tolerance defect
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拟南芥PCNA1和PCNA2在弥补酵母DNA损伤耐受缺陷方面的异同

DOI:
10.1016/j.dnarep.2015.02.003
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发表时间:
2015-04-01
期刊:
影响因子:
3.8
通讯作者:
Xiao, Wei
Xiao, Wei
中科院分区:
医学3区
文献类型:
--
作者:
Xue, Chenyu;Liang, Ke;Xiao, Wei

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增殖细胞核抗原(PCNA)形成同源三聚体,其功能为基因组DNA复制所必需的滑动钳。它还直接参与细胞对DNA损伤反应的调节,这通常是通过其共价修饰来实现的。拟南芥基因组编码两个只有9个氨基酸变异的PCNAs,但最近的两份报告表明,AtPCNA2在DNA损伤反应中比AtPCNA1发挥更关键的作用。本研究发现,这两种atpcna都能在功能上补充酵母POL30 (PCNA)的重要作用,但未能挽救POL30的DNA损伤耐受缺陷。令人惊讶的是,AtPCNA1-K164R突变使细胞对DNA损伤更具耐受性,这似乎依赖于PCNA酰化而不是泛素化。在AtPCNAs中发现了两个位于K164结构近端的关键残基,它们导致了DNA损伤耐受性的差异,因为它们的氨基酸取代改变了DNA损伤耐受性的水平。综上所述,这两种AtPCNAs在泛素化和summoylation方面的效率不同,导致它们对酵母细胞DNA损伤的不同反应。(C) 2015 Elsevier B.V.版权所有
Proliferating cell nuclear antigen (PCNA) forms a homotrimer that functions as a sliding clamp essential for genomic DNA replication. It is also directly involved in the regulation of cellular response to DNA damage, which is typically achieved through its covalent modifications. The Arabidopsis genome encodes two PCNAs with only nine amino acid variations, yet two recent reports indicate that AtPCNA2 plays a more critical role in DNA damage response than AtPCNA1. In this study, it was found that both AtPCNAs were able to functionally complement the essential roles of yeast POL30 (PCNA), but failed to rescue the DNA damage tolerance defect of pol30. Surprisingly, the AtPCNA1-K164R mutation rendered cells more tolerant to DNA damage, which appears to be dependent on PCNA sumoylation but not ubiquitination. Two critical residues proximal in structure to K164 were identified in AtPCNAs that contribute to their differences in DNA damage tolerance, since their amino acid substitutions alter the level of DNA damage tolerance. Collectively, it is concluded that the two AtPCNAs differ in their efficiency for ubiquitination and sumoylation, leading to their differential responses to DNA damage in yeast cells. (C) 2015 Elsevier B.V. All rights reserved.