The ATR-WEE1 kinase module promotes SUPPRESSOR OF GAMMA RESPONSE 1 translation to activate replication stress responses

文献类型： 外文期刊

第一作者： Chen, Hanchen

作者： Chen, Hanchen;Pan, Ting;Zheng, Xueao;Huang, Yongchi;Wu, Chong;Yang, Tongbin;Gao, Shan;Wang, Lili;Yan, Shunping;Chen, Hanchen;Pan, Ting;Zheng, Xueao;Huang, Yongchi;Wu, Chong;Yang, Tongbin;Gao, Shan;Wang, Lili;Yan, Shunping;Chen, Hanchen;Pan, Ting;Zheng, Xueao;Huang, Yongchi;Wu, Chong;Yang, Tongbin;Gao, Shan;Wang, Lili;Yan, Shunping;Chen, Hanchen;Pan, Ting;Zheng, Xueao;Huang, Yongchi;Wu, Chong;Yang, Tongbin;Gao, Shan;Wang, Lili;Yan, Shunping;Chen, Hanchen;Pan, Ting;Zheng, Xueao;Huang, Yongchi;Wu, Chong;Yang, Tongbin;Gao, Shan;Wang, Lili;Yan, Shunping

作者机构：

期刊名称：PLANT CELL （ 影响因子：11.6； 五年影响因子：12.9 ）

ISSN： 1040-4651

年卷期： 2023 年 35 卷 8 期

页码：

收录情况： SCI

摘要： DNA replication stress threatens genome stability and is a hallmark of cancer in humans. The evolutionarily conserved kinases ATR (ATM and RAD3-related) and WEE1 are essential for the activation of replication stress responses. Translational control is an important mechanism that regulates gene expression, but its role in replication stress responses is largely unknown. Here we show that ATR-WEE1 control the translation of SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1), a master transcription factor required for replication stress responses in Arabidopsis thaliana. Through genetic screening, we found that the loss of GENERAL CONTROL NONDEREPRESSIBLE 20 (GCN20) or GCN1, which function together to inhibit protein translation, suppressed the hypersensitivity of the atr or wee1 mutant to replication stress. Biochemically, WEE1 inhibits GCN20 by phosphorylating it; phosphorylated GCN20 is subsequently polyubiquitinated and degraded. Ribosome profiling experiments revealed that that loss of GCN20 enhanced the translation efficiency of SOG1, while overexpressing GCN20 had the opposite effect. The loss of SOG1 reduced the resistance of wee1 gcn20 to replication stress, whereas overexpressing SOG1 enhanced the resistance to atr or wee1 to replication stress. These results suggest that ATR-WEE1 inhibits GCN20-GCN1 activity to promote the translation of SOG1 during replication stress. These findings link translational control to replication stress responses in Arabidopsis. The ATR-WEE1 kinase-mediated activation of SUPPRESSOR OF GAMMA RESPONSE 1 translation links translational control to replication stress responses in Arabidopsis.

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