Cell-cycle regulation of non-enzymatic functions of the Drosophila methyltransferase PR-Set7

Autor: Zouaz, Amel, Fernando, Céline, Perez, Yannick, Sardet, Claude, Julien, Eric, Grimaud, Charlotte
Přispěvatelé: Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Herrada, Anthony
Jazyk: angličtina
Rok vydání: 2018
Předmět:
MESH: G1 Phase Cell Cycle Checkpoints
MESH: Mutation
MESH: Drosophila Proteins
Ubiquitin-Protein Ligases
Cell Cycle Proteins
MESH: Proteolysis
[SDV.CAN]Life Sciences [q-bio]/Cancer
Cell Line
MESH: Chromatin
MESH: Drosophila melanogaster
Animals
Genetically Modified
Histones
MESH: Animals
Genetically Modified
MESH: Interphase
MESH: Cell Cycle Proteins
[SDV.CAN] Life Sciences [q-bio]/Cancer
Proliferating Cell Nuclear Antigen
Animals
Drosophila Proteins
MESH: Protein Binding
MESH: Animals
Interphase
MESH: Histones
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
Gene regulation
Chromatin and Epigenetics
MESH: Histone-Lysine N-Methyltransferase
Histone-Lysine N-Methyltransferase
G1 Phase Cell Cycle Checkpoints
MESH: Ubiquitin-Protein Ligases
Chromatin
MESH: Cell Line
Drosophila melanogaster
MESH: Proliferating Cell Nuclear Antigen
MESH: Protein Processing
Post-Translational
Mutation
Proteolysis
Protein Processing
Post-Translational
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Protein Binding
Zdroj: Nucleic Acids Research
Nucleic Acids Research, Oxford University Press, 2018, 46 (6), pp.2834-2849. ⟨10.1093/nar/gky034⟩
ISSN: 0305-1048
1362-4962
DOI: 10.1093/nar/gky034⟩
Popis: International audience; Tight cell-cycle regulation of the histone H4-K20 methyltransferase PR-Set7 is essential for the maintenance of genome integrity. In mammals, this mainly involves the interaction of PR-Set7 with the replication factor PCNA, which triggers the degradation of the enzyme by the CRL4CDT2 E3 ubiquitin ligase. PR-Set7 is also targeted by the SCFβ-TRCP ligase, but the role of this additional regulatory pathway remains unclear. Here, we show that Drosophila PR-Set7 undergoes a cell-cycle proteolytic regulation, independently of its interaction with PCNA. Instead, Slimb, the ortholog of β-TRCP, is specifically required for the degradation of the nuclear pool of PR-Set7 prior to S phase. Consequently, inactivation of Slimb leads to nuclear accumulation of PR-Set7, which triggers aberrant chromatin compaction and G1/S arrest. Strikingly, these phenotypes result from non-enzymatic PR-Set7 functions that prevent proper histone H4 acetylation independently of H4K20 methylation. Altogether, these results identify the Slimb-mediated PR-Set7 proteolysis as a new critical regulatory mechanism required for proper interphase chromatin organization at G1/S transition.
Databáze: OpenAIRE
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