MORC3 Forms Nuclear Condensates through Phase Separation.

Autor:	Zhang Y; Department of Pharmacology, University of Colorado School of Medicine, 12801 East 17th Avenue, Aurora, CO 80045, USA., Bertulat B; Department of Biology, Technische Universität Darmstadt, Darmstadt, 64287, Germany., Tencer AH; Department of Pharmacology, University of Colorado School of Medicine, 12801 East 17th Avenue, Aurora, CO 80045, USA., Ren X; Department of Chemistry, University of Colorado, Denver, CO 80217, USA., Wright GM; Department of Pharmacology, University of Colorado School of Medicine, 12801 East 17th Avenue, Aurora, CO 80045, USA., Black J; Department of Pharmacology, University of Colorado School of Medicine, 12801 East 17th Avenue, Aurora, CO 80045, USA., Cardoso MC; Department of Biology, Technische Universität Darmstadt, Darmstadt, 64287, Germany., Kutateladze TG; Department of Pharmacology, University of Colorado School of Medicine, 12801 East 17th Avenue, Aurora, CO 80045, USA. Electronic address: tatiana.kutateladze@ucdenver.edu.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2019 Jul 26; Vol. 17, pp. 182-189. Date of Electronic Publication: 2019 Jun 25.
DOI:	10.1016/j.isci.2019.06.030
Abstrakt:	Phase separation can produce local structures with specific functionality in the cell, and in the nucleus, this can lead to chromatin reorganization. Microrchidia 3 (MORC3) is a human ATPase that has been implicated in autoimmune disorders and cancer. Here, we show that MORC3 forms phase-separated condensates with liquid-like properties in the cell nucleus. Fluorescence live-cell imaging reveals that the MORC3 condensates are heterogeneous and undergo dynamic morphological changes during the cell cycle. The ATPase activity of MORC3 drives its phase separation in vitro and requires DNA binding and releasing the MORC3 CW domain-dependent autoinhibition through association with histone H3. Our findings suggest a mechanism by which the ATPase function of MORC3 mediates MORC3 nuclear compartmentalization. (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu