Protein kinase ATR inhibits E3 ubiquitin ligase CRL4PRL1 to stabilize ribonucleotide reductase in response to replication stress

Weiyi Bao; Weijia Zhang; Yongchi Huang; Yan Zhao; Cong Wu; Leilei Duan; Lili Wang; Shunping Yan

Cell Reports (Jul 2023)

Protein kinase ATR inhibits E3 ubiquitin ligase CRL4PRL1 to stabilize ribonucleotide reductase in response to replication stress

Weiyi Bao,
Weijia Zhang,
Yongchi Huang,
Yan Zhao,
Cong Wu,
Leilei Duan,
Lili Wang,
Shunping Yan

Affiliations

Weiyi Bao: Hubei Hongshan Laboratory, Wuhan, Hubei 430070, China; College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen 518000, China; Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Shenzhen 518000, China; Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518000, China
Weijia Zhang: Hubei Hongshan Laboratory, Wuhan, Hubei 430070, China; College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen 518000, China; Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Shenzhen 518000, China; Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518000, China
Yongchi Huang: Hubei Hongshan Laboratory, Wuhan, Hubei 430070, China; College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen 518000, China; Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Shenzhen 518000, China; Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518000, China
Yan Zhao: Hubei Hongshan Laboratory, Wuhan, Hubei 430070, China; College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen 518000, China; Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Shenzhen 518000, China; Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518000, China
Cong Wu: Hubei Hongshan Laboratory, Wuhan, Hubei 430070, China; College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen 518000, China; Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Shenzhen 518000, China; Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518000, China
Leilei Duan: Hubei Hongshan Laboratory, Wuhan, Hubei 430070, China; College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen 518000, China; Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Shenzhen 518000, China; Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518000, China
Lili Wang: Hubei Hongshan Laboratory, Wuhan, Hubei 430070, China; College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen 518000, China; Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Shenzhen 518000, China; Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518000, China; Corresponding author
Shunping Yan: Hubei Hongshan Laboratory, Wuhan, Hubei 430070, China; College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen 518000, China; Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Shenzhen 518000, China; Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518000, China; Corresponding author

Journal volume & issue: Vol. 42, no. 7
p. 112685

Abstract

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Summary: The protein kinase ATR is essential for replication stress responses in all eukaryotes. Ribonucleotide reductase (RNR) catalyzes the formation of deoxyribonucleotide (dNTP), the universal building block for DNA replication and repair. However, the relationship between ATR and RNR is not well understood. Here, we show that ATR promotes the protein stability of RNR in Arabidopsis. Through an activation tagging-based genetic screen, we found that overexpression of TSO2, a small subunit of RNR, partially suppresses the hypersensitivity of the atr mutant to replication stress. Biochemically, TSO2 interacts with PRL1, a central subunit of the Cullin4-based E3 ubiquitin ligase CRL4PRL1, which polyubiquitinates TSO2 and promotes its degradation. ATR inhibits CRL4PRL1 to attenuate TSO2 degradation. Our work provides an important insight into the replication stress responses and a post-translational regulatory mechanism for RNR. Given the evolutionary conservation of the proteins involved, the ATR-PRL1-RNR module may act across eukaryotes.

CP: Molecular biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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