SPOP mutation induces replication over-firing by impairing Geminin ubiquitination and triggers replication catastrophe upon ATR inhibition

Jian Ma; Qing Shi; Gaofeng Cui; Haoyue Sheng; Maria Victoria Botuyan; Yingke Zhou; Yuqian Yan; Yundong He; Liguo Wang; Yuzhuo Wang; Georges Mer; Dingwei Ye; Chenji Wang; Haojie Huang

doi:10.1038/s41467-021-26049-6

Nature Communications (Oct 2021)

SPOP mutation induces replication over-firing by impairing Geminin ubiquitination and triggers replication catastrophe upon ATR inhibition

Jian Ma,
Qing Shi,
Gaofeng Cui,
Haoyue Sheng,
Maria Victoria Botuyan,
Yingke Zhou,
Yuqian Yan,
Yundong He,
Liguo Wang,
Yuzhuo Wang,
Georges Mer,
Dingwei Ye,
Chenji Wang,
Haojie Huang

Affiliations

Jian Ma: Department of Urology, Fudan University Shanghai Cancer Center
Qing Shi: State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University
Gaofeng Cui: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science
Haoyue Sheng: Department of Urology, Fudan University Shanghai Cancer Center
Maria Victoria Botuyan: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science
Yingke Zhou: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science
Yuqian Yan: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science
Yundong He: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science
Liguo Wang: Divison of Computational Biology, Mayo Clinic College of Medicine and Science
Yuzhuo Wang: Department of Experimental Therapeutics, BC Cancer Research Centre
Georges Mer: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science
Dingwei Ye: Department of Urology, Fudan University Shanghai Cancer Center
Chenji Wang: State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University
Haojie Huang: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science

DOI: https://doi.org/10.1038/s41467-021-26049-6
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 14

Abstract

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Geminin-Cdt1 plays essential roles in the regulation of DNA replication. Here the authors reveal that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP prevents DNA replication over-firing and genome instability by affecting Geminin ubiquitination.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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