Chromodomain on Y-like 2 (CDYL2) implicated in mitosis and genome stability regulation via interaction with CHAMP1 and POGZ.


Journal

Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402

Informations de publication

Date de publication:
20 Jan 2023
Historique:
received: 16 06 2022
accepted: 29 11 2022
revised: 28 11 2022
entrez: 19 1 2023
pubmed: 20 1 2023
medline: 24 1 2023
Statut: epublish

Résumé

Histone H3 trimethylation on lysine 9 (H3K9me3) is a defining feature of mammalian pericentromeres, loss of which results in genome instability. Here we show that CDYL2 is recruited to pericentromeres in an H3K9me3-dependent manner and is required for faithful mitosis and genome stability. CDYL2 RNAi in MCF-7 breast cancer cells and Hela cervical cancer cells inhibited their growth, induced apoptosis, and provoked both nuclear and mitotic aberrations. Mass spectrometry analysis of CDYL2-interacting proteins identified the neurodevelopmental disease-linked mitotic regulators CHAMP1 and POGZ, which are associated with a central non-conserved region of CDYL2. RNAi rescue assays identified both the CDYL2 chromodomain and the CHAMP1-POGZ interacting region as required and, together, sufficient for CDYL2 regulation of mitosis and genome stability. CDYL2 RNAi caused loss of CHAMP1 localization at pericentromeres. We propose that CDYL2 functions as an adaptor protein that connects pericentromeric H3K9me3 with CHAMP1 and POGZ to ensure mitotic fidelity and genome stability.

Identifiants

pubmed: 36658409
doi: 10.1007/s00018-022-04659-7
pii: 10.1007/s00018-022-04659-7
doi:

Substances chimiques

CHAMP1 protein, human 0
Chromosomal Proteins, Non-Histone 0
Histones 0
Lysine K3Z4F929H6
Phosphoproteins 0
CDYL2 protein, human 0
Co-Repressor Proteins 0
POGZ protein, human 0
Cell Cycle Proteins 0
DNA-Binding Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

47

Subventions

Organisme : Institut National Du Cancer
ID : PLBIO2016-180

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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Auteurs

Maha Siouda (M)

Centre Léon Bérard, Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Lyon, France.

Audrey D Dujardin (AD)

Centre Léon Bérard, Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Lyon, France.

Blanche Dekeyzer (B)

Centre Léon Bérard, Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Lyon, France.

Laurent Schaeffer (L)

Faculté de Médecine, Physiopathology and Genetics of Neurons and Muscles Division, Institut NeuroMyoGène, Université Claude Bernard Lyon 1, Université de Lyon, INSERM U1217, CNRS, UMR5310, 3ème étage, Aile B, 8 Avenue Rockefeller, 69008, Lyon, France.
Centre de Biotechnologie Cellulaire, CBC Biotec, CHU de Lyon - HCL Groupement Est, 59 Bvd Pinel, 69677, Cedex Bron, France.

Peter Mulligan (P)

Centre Léon Bérard, Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Lyon, France. peter.mulligan@inserm.fr.
Faculté de Médecine, Physiopathology and Genetics of Neurons and Muscles Division, Institut NeuroMyoGène, Université Claude Bernard Lyon 1, Université de Lyon, INSERM U1217, CNRS, UMR5310, 3ème étage, Aile B, 8 Avenue Rockefeller, 69008, Lyon, France. peter.mulligan@inserm.fr.

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