Genetic screening identifies a SUMO protease dynamically maintaining centromeric chromatin

Sreyoshi Mitra, Dani L. Bodor, Ana F. David, Izma Abdul-Zani, João F. Mata, Beate Neumann, Sabine Reither, Christian Tischer and Lars E. T. Jansen ()
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Sreyoshi Mitra: University of Oxford
Dani L. Bodor: Instituto Gulbenkian de Ciência
Ana F. David: Instituto Gulbenkian de Ciência
Izma Abdul-Zani: University of Oxford
João F. Mata: Instituto Gulbenkian de Ciência
Beate Neumann: European Molecular Biology Laboratory (EMBL)
Sabine Reither: European Molecular Biology Laboratory (EMBL)
Christian Tischer: European Molecular Biology Laboratory (EMBL)
Lars E. T. Jansen: University of Oxford

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-019-14276-x

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