PRE-SET7-DIRECTED LYSINE METHLATION PATHWAYS / FROM CELL-CYCLE REGULATION TO CANCER MECHANISMS

Orateur : Eric JULIEN (IRCM, Montpellier)

To ensure accurate inheritance of genetic information through cell proliferation, chromosomes must be precisely copied only during S phase, and then correctly condensed and segregated during mitosis. Several findings from our group and others have shown that this chromosome cycle is in part controlled by cell-cycle regulated chromatin modifications, in particular due to changing activity of the lysine methyltransferase PRSet7/ SET8 responsible for the monomethylation of histone H4 at lysine 20. Cell cycle oscillation of PR-Set7 is orchestrated by ubiquitin-mediated proteolysis, and interference with this regulatory process leads to muliple cell cycle defects, including unscheduled licensing of replication origins and altered timing in chromatin compaction process. We will present our last data and discuss the mechanisms by which PRSet7- mediated lysine methylation signaling regulates genome stability and may have an impact in cancer pathways.

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