Sml1 Inhibits the DNA Repair Activity of Rev1 in Saccharomyces cerevisiae during Oxidative Stress
Sml1 Inhibits the DNA Repair Activity of Rev1 in Saccharomyces cerevisiae during Oxidative Stress
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Sml1 在氧化应激过程中抑制酿酒酵母 Rev1 的 DNA 修复活性
DOI：
10.1128/aem.02838-19
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发表时间：
2020-01
影响因子：
4.4
通讯作者：
Jing Wu
中科院分区：
文献类型：
--
作者：
Rui Yao;Pei Zhou;Chengjin Wu;Liming Liu;Jing Wu
在酿酒酵母中，Y家族DNA聚合酶Rev 1通过跨损伤DNA合成（TLS）参与DNA损伤的修复。本研究旨在阐明Rev 1在氧化应激诱导的S.在酿酒酵母中，REV 1被删除并过表达;对这些突变体和野生型菌株进行沿着的转录组分析，以筛选在DNA损伤应答过程中可能与REV 1相关的潜在基因。当酵母细胞用2 mM H2 O2处理时，与野生型菌株的存活率和突变频率相比，REV 1的缺失分别导致存活率和突变频率降低1.5倍和2.8倍，而REV 1的过表达分别使存活率和突变频率增加1.1倍和2.9倍。转录组和表型分析表明Sml 1通过抑制Rev 1的活性而加重了酵母细胞中的氧化应激。这种抑制作用是由于Rev 1的BRCA 1 C末端（BRCT）结构域与Sml 1的氨基酸残基36至70之间的物理相互作用;当这种相互作用被阻断时，细胞存活率和突变频率分别增加了1.8倍和3.1倍。我们还发现，Sml 1抑制Rev 1的磷酸化氧化应激和SML 1的删除增加了46%的Rev 1的磷酸化，而过度表达的SML 1减少Rev 1的磷酸化。总之，这些研究结果表明Sml 1可能是一种新的调节因子，在氧化应激过程中介导Rev 1去磷酸化以抑制其活性。在氧化应激（2 mM H2 O2）条件下，REV 1的缺失导致细胞严重生长缺陷。此外，我们发现Sml 1与Rev 1物理相互作用并抑制Rev 1磷酸化，从而抑制Rev 1 DNA抗氧化活性。这些结果表明，Sml 1可能是一种新的调节器Rev 1在响应DNA损伤的氧化应激。
In Saccharomyces cerevisiae, Y family DNA polymerase Rev1 is involved in the repair of DNA damage by translesion DNA synthesis (TLS). In the current study, to elucidate the role of Rev1 in oxidative stress-induced DNA damage in S. cerevisiae,REV1was deleted and overexpressed; transcriptome analysis of these mutants along with the wild-type strain was performed to screen potential genes that could be associated withREV1during response to DNA damage. When the yeast cells were treated with 2 mM H2O2, the deletion ofREV1resulted in a 1.5- and 2.8-fold decrease in the survival rate and mutation frequency, respectively, whereas overexpression ofREV1increased the survival rate and mutation frequency by 1.1- and 2.9-fold, respectively, compared to the survival rate and mutation frequency of the wild-type strain. Transcriptome and phenotypic analyses identified that Sml1 aggravated oxidative stress in the yeast cells by inhibiting the activity of Rev1. This inhibition was due to the physical interaction between the BRCA1 C terminus (BRCT) domain of Rev1 and amino acid residues 36 to 70 of Sml1; the cell survival rate and mutation frequency increased by 1.8- and 3.1-fold, respectively, when this interaction was blocked. We also found that Sml1 inhibited Rev1 phosphorylation under oxidative stress and that deletion ofSML1increased the phosphorylation of Rev1 by 46%, whereas overexpression ofSML1reduced phosphorylation of Rev1. Overall, these findings demonstrate that Sml1 could be a novel regulator that mediates Rev1 dephosphorylation to inhibit its activity during oxidative stress.IMPORTANCERev1 was critical for cell growth in S. cerevisiae, and the deletion ofREV1caused a severe growth defect in cells exposed to oxidative stress (2 mM H2O2). Furthermore, we found that Sml1 physically interacted with Rev1 and inhibited Rev1 phosphorylation, thereby inhibiting Rev1 DNA antioxidant activity. These findings indicate that Sml1 could be a novel regulator for Rev1 in response to DNA damage by oxidative stress.
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.0902175106
发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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