A Nucleolus-Localized Activator of Cdc14 Phosphatase Supports rDNA Segregation in Yeast Mitosis.

摘要

Cdc14 phosphatase is an important regulator of mitosis in budding yeast [1]. Cdc14 antagonizes cyclin-dependent kinases and promotes multiple postmetaphase events, including segregation of the ribosomal RNA gene array (rDNA) and the nucleolus assembled around this gene cluster [2-6]. During most of the cell cycle, Cdc14 is anchored to the nucleolus and kept inactive by binding to Net1 (also known as Cfi1) [7-9]. Cdc14 and Net1 are part of a larger nucleolar-protein network, which also contains the Net1-related protein Tof2 [10-12]. Tof2 contributes to the transcriptional silencing of rDNA regions [12], but the precise cellular and molecular functions of Tof2 remain unclear. Here, we report that, like Net1, Tof2 can bind to Cdc14 directly. Unlike Net1, however, Tof2 did not inhibit Cdc14 but supported Cdc14 phosphatase activity and in vivo function. Deletion of TOF2 delayed rDNA segregation with little effect on mitotic exit, impaired relocalization of condensin to the nucleolus in anaphase, and caused rDNA-dependent synthetic lethality when a cdc14 mutation was present. Thus, Tof2 collaborates with Cdc14 specifically in rDNA segregation, presumably by targeting Cdc14 phosphatase activity to the nucleolus during anaphase to support resolution and compaction of this repetitive and highly transcribed DNA locus.