Non-canonical role for the BAF complex subunit DPF3 in mitosis and ciliogenesis

Author:

Verrillo Giulia1ORCID,Obeid Anna Maria1,Genco Alexia1,Scrofani Jacopo2,Orange François3,Hanache Sarah1,Mignon Julien4,Leyder Tanguy4,Michaux Catherine4,Kempeneers Céline567,Bricmont Noëmie567,Herkenne Stephanie8,Vernos Isabelle2910,Martin Maud11,Mottet Denis1ORCID

Affiliation:

1. University of Liege, GIGA – Research Institute 1 , Molecular Analysis of Gene Expression (MAGE) Laboratory, B34, Avenue de l'Hôpital, B-4000 Liège , Belgium

2. Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology 2 , Barcelona 08003 , Spain

3. Université Côte d'Azur, Centre Commun de Microscopie Appliquée (CCMA) 3 , 06100 Nice , France

4. University of Namur 4 , Laboratory of Physical Chemistry of Biomolecules, Unité de Chimie Physique Théorique et Structurale (UCPTS), Rue de Bruxelles 61, B-5000 Namur , Belgium

5. University of Liege 5 , Pneumology Laboratory , , B-4000 Liège , Belgium

6. I3 Group, GIGA Research Center 5 , Pneumology Laboratory , , B-4000 Liège , Belgium

7. University Hospital Liège 6 Division of Respirology, Department of Pediatrics , , B-4000 Liège , Belgium

8. University of Liege, GIGA-Cancer 7 , Laboratory of Mitochondria and Cell Communication, B34, Avenue de l'Hôpital, B-4000 Liège , Belgium

9. Universitat Pompeu Fabra (UPF) 8 , Barcelona 08002 , Spain

10. ICREA, Pg. Lluis Companys 23 9 , Barcelona 08010 , Spain

11. ULB Neuroscience Institute, Université libre de Bruxelles 10 Laboratory of Neurovascular Signaling, Department of Molecular Biology , , B-6041 Gosselies , Belgium

Abstract

ABSTRACT DPF3, along with other subunits, is a well-known component of the BAF chromatin remodeling complex, which plays a key role in regulating chromatin remodeling activity and gene expression. Here, we elucidated a non-canonical localization and role for DPF3. We showed that DPF3 dynamically localizes to the centriolar satellites in interphase and to the centrosome, spindle midzone and bridging fiber area, and midbodies during mitosis. Loss of DPF3 causes kinetochore fiber instability, unstable kinetochore–microtubule attachment and defects in chromosome alignment, resulting in altered mitotic progression, cell death and genomic instability. In addition, we also demonstrated that DPF3 localizes to centriolar satellites at the base of primary cilia and is required for ciliogenesis by regulating axoneme extension. Taken together, these findings uncover a moonlighting dual function for DPF3 during mitosis and ciliogenesis.

Funder

Sanofi

Fonds De La Recherche Scientifique – FNRS

Télévie

Fonds Léon Fredericq

Fonds Spéciaux de Recherche

Ministerio de Economía y Competitividad

Ministerio de Ciencia, Innovación y Universidades

Generalitat de Catalunya

Publisher

The Company of Biologists

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