Polo kinase Cdc5 is a central regulator of meiosis I

Abstract

During meiosis, two consecutive rounds of chromosome segregation yield four haploid gametes from one diploid cell. The Polo kinase Cdc5 is required for meiotic progression, but how Cdc5 coordinates multiple cell-cycle events during meiosis I is not understood. Here we show that CDC5-dependent phosphorylation of Rec8, a subunit of the cohesin complex that links sister chromatids, is required for efficient cohesin removal from chromosome arms, which is a prerequisite for meiosis I chromosome segregation. CDC5 also establishes conditions for centromeric cohesin removal during meiosis II by promoting the degradation of Spo13, a protein that protects centromeric cohesin during meiosis I. Despite CDC5's central role in meiosis I, the protein kinase is dispensable during meiosis II and does not even phosphorylate its meiosis I targets during the second meiotic division. We conclude that Cdc5 has evolved into a master regulator of the unique meiosis I chromosome segregation pattern.P olo kinases are central regulators of chromosome segregation and control multiple mitotic events (1). Budding yeast contains a single Polo kinase, CDC5. Unlike in higher eukaryotes, budding yeast CDC5 primarily regulates postmetaphase events, its essential function being to trigger exit from mitosis (2). CDC5 also contributes to the efficient inactivation of cohesins, the protein complexes that hold sister chromatids together until the onset of chromosome segregation. Cdc5 phosphorylates the cohesin subunit Mcd1/Scc1 to facilitate its cleavage by the protease separase (3).CDC5 also regulates the specialized cell division that gives rise to gametes, known as meiosis (4). During meiosis, two consecutive rounds of chromosome segregation follow one round of DNA replication. During meiosis I, homologous chromosomes segregate; during meiosis II, sister chromatids separate (5). The chromosome segregation machinery is modified in three ways to facilitate the unusual meiosis I division. First, the combination of homologous recombination and cohesin complexes distal to the resulting cross-overs mediate the physical linkage of homologous chromosomes, which is essential for their accurate segregation during meiosis I. Second, sister chromatids of each homolog must be segregated to the same pole rather than to opposite poles, as they are during mitosis. The fusion of sister kinetochores by co-orientation factors (the monopolin complex in yeast) facilitates the attachment of microtubules emanating from one spindle pole. Third, cohesin complexes must be lost in a stepwise manner from chromosomes. During meiosis I cohesin complexes are lost from chromosome arms to bring about the segregation of homologous chromosomes (6). The residual cohesins at centromeres facilitate the accurate segregation of sister chromatids during meiosis II. Cdc5 has been implicated in the execution of all three meiosis I-specific events. CDC5 is required for the resolution of double Holliday junctions during homologous recombination (7,8). Cdc5 also controls the co-orientation of ...

Identification of cell-specific targets of sumoylation during mouse spermatogenesis

“…In yeast, CDC5 is also involved in the regulation of the SUMO pathway and modulates the maintenance and dissolution of cohesion at centromeres (Baldwin et al . 2009, Attner et al . 2013).…”

Systematic Analysis of the Phosphoproteome and Kinase-substrate Networks in the Mouse Testis

“…In fact, Jordan et al have discovered the great importance of PLKs in synaptonemal complex disassembly in mouse spermatocytes by brief in vitro culture of spermatocytes (12). Recently, Cdc5, an ortholog of the PLKs, was found to be a central regulator of meiosis I in yeast (59). Taking these various points into consideration, it is proposed that the PLKs are critical for spermatogenesis.…”

Meiotic prophase roles of Rec8 in crossover recombination and chromosome structure

“…Casein kinase 1δ/ϵ (CK1δ/ϵ, Hrr25 in yeast) and Dbf4-dependent Cdc7 kinase (DDK) collaboratively account for Rec8 phosphorylation in early/mid-prophase (9). Polo-like kinase (‘PLK’; Cdc5 in yeast) can also phosphorylate Rec8 (24–26). Cdc5 is activated in mid/late prophase and has roles in the late prophase stages of recombination (27) and in cohesin removal at the prophase-to-metaphase transition (11).…”