Sufu negatively regulates both initiations of centrosome duplication and DNA replication

The initiations of both DNA replication and centrosome duplication are strictly coordinated during the cell cycle, and failure to do so will damage the cell or induce centrosome amplification and genome instability. Here, we report that Sufu inhibits centrosome duplication via facilitating CP110 phosphorylation and suppresses DNA replication via promoting intranuclear Cdt1 degradation and expelling prereplication complex (pre-RC) components from chromosomes. Elimination of inhibitory Sufu from the centrosome counts on vesicle release at the ciliary tip, and, from the nucleus, it relies on protein degradation. This work reveals a mechanism through which Sufu, which acts as a “master switch,” negatively regulates both initiations of DNA replication and centrosome duplication, and it may shed light on the preparation step control of cell proliferation.