Genetic screening identifies a SUMO protease dynamically maintaining centromeric chromatin

Nat Commun. 2020 Jan 24;11(1):501. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • Cell Cycle
  • Centromere / metabolism*
  • Centromere Protein A / metabolism
  • Chromatin / metabolism*
  • Cysteine Endopeptidases / metabolism*
  • Genetic Testing*
  • Genotype
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism
  • Protein Subunits / metabolism
  • Proteolysis
  • Sumoylation


  • Centromere Protein A
  • Chromatin
  • Protein Subunits
  • Cysteine Endopeptidases
  • SENP6 protein, human