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

• Published in: Nature communications Vol. 12; no. 1; pp. 5779 - 14
• Main Authors: Ma, Jian, Shi, Qing, Cui, Gaofeng, Sheng, Haoyue, Botuyan, Maria Victoria, Zhou, Yingke, Yan, Yuqian, He, Yundong, Wang, Liguo, Wang, Yuzhuo, Mer, Georges, Ye, Dingwei, Wang, Chenji, Huang, Haojie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 14/63; 45/70; 631/337/151; 631/337/458/582; 631/45/612/1244; 631/67/395; 64/60; 82/58; Adapters; Animals; BASIC BIOLOGICAL SCIENCES; Cancer; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell death; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA replication; DNA Replication - genetics; DNA Replication - physiology; Geminin; Geminin - genetics; Geminin - metabolism; Genomes; Genomic instability; Humanities and Social Sciences; Humans; Lysine; Male; MCM protein; Mice; Mice, SCID; Minichromosome Maintenance Proteins - genetics; Minichromosome Maintenance Proteins - metabolism; multidisciplinary; Mutation; Mutation - genetics; Nuclear Proteins - genetics; Oncogenes; Proteins; Replication; Replication origins; Repressor Proteins - genetics; Science; Science (multidisciplinary); Tumor suppressor genes; Tumorigenesis; Tumors; Tumour-suppressor proteins; Ubiquitin; Ubiquitin-protein ligase; Ubiquitin-Protein Ligase Complexes - genetics; Ubiquitination; Ubiquitination - genetics; Ubiquitination - physiology; Ubiquitylation; Unwinding; Yeast
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-26049-6

Geminin and its binding partner Cdt1 are essential for the regulation of DNA replication. Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at...