Genetic screening identifies a SUMO protease dynamically maintaining centromeric chromatin

• Published in: Nature communications Vol. 11; no. 1; p. 501
• Main Authors: Mitra, Sreyoshi, Bodor, Dani L., David, Ana F., Abdul-Zani, Izma, Mata, João F., Neumann, Beate, Reither, Sabine, Tischer, Christian, Jansen, Lars E. T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.01.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/1; 14/35; 14/63; 42/34; 42/89; 49/47; 631/208/176; 631/337/103/90; 631/45/612/1252; 631/80/103; 631/80/641; Biocatalysis; Cell Cycle; Centromere - metabolism; Centromere Protein A - metabolism; Centromeres; Chromatin; Chromatin - metabolism; Control stability; Cysteine Endopeptidases - metabolism; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA repair; Genetic screening; Genetic Testing; Genotype; HeLa Cells; Heredity; Histone H3; Humanities and Social Sciences; Humans; Kinetochores - metabolism; Maintenance; multidisciplinary; Nucleosomes; Protease; Protein Subunits - metabolism; Proteinase; Proteolysis; Regulators; Science; Science (multidisciplinary); Self propagation; SUMO protein; Sumoylation; Transcription
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-14276-x

Centromeres are defined by a self-propagating chromatin structure based on stable inheritance of CENP-A containing nucleosomes. Here, we present a genetic screen coupled to pulse-chase labeling that allow us to identify proteins selectively involved in deposition of nascent CENP-A or in long-term transmission of chromatin-bound CENP-A. These include factors with known roles in DNA replication, repair, chromatin modification, and transcription, revealing a broad set of chromatin regulators that impact on CENP-A dynamics. We further identify the SUMO-protease SENP6 as a key factor, not only controlling CENP-A stability but virtually the entire centromere and kinetochore. Loss of SENP6 results in hyper-SUMOylation of CENP-C and CENP-I but not CENP-A itself. SENP6 activity is required throughout the cell cycle, suggesting that a dynamic SUMO cycle underlies a continuous surveillance of the centromere complex that in turn ensures stable transmission of CENP-A chromatin. Centromeres are a self-propagating chromatin structure that feature nucleosomes containing histone H3 variant CENP-A. Here, the authors screen for factors that play a role in CENP-A chromatin maintenance, finding that SUMO-protease SENP6 controls inheritance of chromatin bound CENP-A and is required for the maintenance of the centromere and kinetochore complex.