O-GlcNAc transferase associates with the MCM2–7 complex and its silencing destabilizes MCM–MCM interactions

Maïté Leturcq, Marlène Mortuaire, Stéphan Hardivillé, Céline Schulz, Tony Lefebvre, Anne Sophie Vercoutter-Edouart

Research output: Contribution to journalArticle

Abstract

O-GlcNAcylation of proteins is governed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). The homeostasis of O-GlcNAc cycling is regulated during cell cycle progression and is essential for proper cellular division. We previously reported the O-GlcNAcylation of the minichromosome maintenance proteins MCM2, MCM3, MCM6 and MCM7. These proteins belong to the MCM2–7 complex which is crucial for the initiation of DNA replication through its DNA helicase activity. Here we show that the six subunits of MCM2–7 are O-GlcNAcylated and that O-GlcNAcylation of MCM proteins mainly occurs in the chromatin-bound fraction of synchronized human cells. Moreover, we identify stable interaction between OGT and several MCM subunits. We also show that down-regulation of OGT decreases the chromatin binding of MCM2, MCM6 and MCM7 without affecting their steady-state level. Finally, OGT silencing or OGA inhibition destabilizes MCM2/6 and MCM4/7 interactions in the chromatin-enriched fraction. In conclusion, OGT is a new partner of the MCM2–7 complex and O-GlcNAcylation homeostasis might regulate MCM2–7 complex by regulating the chromatin loading of MCM6 and MCM7 and stabilizing MCM/MCM interactions.

Original languageEnglish (US)
Pages (from-to)4321-4339
Number of pages19
JournalCellular and Molecular Life Sciences
Volume75
Issue number23
DOIs
StatePublished - Dec 1 2018

Keywords

  • Cell cycle
  • Chromatin
  • DNA replication
  • O-GlcNAcylation
  • Post-translational modification
  • Pre-replicative complex

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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  • Cite this

    Leturcq, M., Mortuaire, M., Hardivillé, S., Schulz, C., Lefebvre, T., & Vercoutter-Edouart, A. S. (2018). O-GlcNAc transferase associates with the MCM2–7 complex and its silencing destabilizes MCM–MCM interactions. Cellular and Molecular Life Sciences, 75(23), 4321-4339. https://doi.org/10.1007/s00018-018-2874-0