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

Abstract:

: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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Zouaz A,Fernando C,Perez Y,Sardet C,Julien E,Grimaud C

doi

10.1093/nar/gky034

subject

Has Abstract

pub_date

2018-04-06 00:00:00

pages

2834-2849

issue

6

eissn

0305-1048

issn

1362-4962

pii

4823210

journal_volume

46

pub_type

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