A knockout screen for protein kinases required for the proper meiotic segregation of chromosomes in the fission yeast Schizosaccharomyces pombe

Abstract

The reduction of chromosome number during meiosis is achieved by two successive rounds of chromosome segregation after just single round of DNA replication. To identify novel proteins required for the proper segregation of chromosomes during meiosis, we analyzed the consequences of deleting Schizosaccharomyces pombe genes predicted to encode protein kinases that are not essential for cell viability. We show that Mph1, a member of the Mps1 family of spindle assembly checkpoint kinases, is required to prevent meiosis I homolog non-disjunction. We also provide evidence for a novel function of Spo4, the fission yeast ortholog of Dbf4-dependent Cdc7 kinase, in regulating the length of anaphase II spindles. In the absence of Spo4, abnormally elongated anaphase II spindles frequently overlap and thus destroy the linear order of nuclei in the ascus. Our observation that the spo4Δ mutant phenotype can be partially suppressed by inhibiting Cdc2-as suggests that dysregulation of the activity of this cyclin-dependent kinase may cause abnormal elongation of anaphase II spindles in spo4Δ mutant cells.

The Gpr1/Zdbf2 locus provides new paradigms for transient and dynamic genomic imprinting in mammals

“…The eponymous DBF4 protein is an activator of the CDC7 serine/threonine kinase, which has a conserved role in DNA replication initiation from yeast to humans (Hughes et al 2012). In yeast, the dbf4/cdc7 complex was moreover linked to chromosome segregation during meiosis (Kovacikova et al 2013;Le et al 2013). Coincidently, we found that Liz expression peaks at meiosis during mouse spermatogenesis, and canonical Zdbf2 is highly transcribed in the oocyte, leading to the exciting possibility that Zdbf2 may fulfill meiotic roles in mammals.…”

Regulation of chromosome dynamics by Hsk1/Cdc7 kinase

“…Spindles for meiosis II are often fragmented in these mutants [14]. In contrast, another recent report showed that abnormally elongated anaphase II spindles frequently overlap and thus destroy the linear order of nuclei in the ascus in the absence of Spo4 or Spo6 [45]. Thus Spo4-Spo6 may have a critical function in regulating the spindle length during meiosis II.…”

Roles of CDK and DDK in Genome Duplication and Maintenance: Meiotic Singularities

“…Spo4 and its regulator Spo6 are expressed exclusively in meiosis, and while Spo4 is dispensable for meiotic replication, it contributes to meiotic chromosome segregation [69]. Consistent with this, its absence only affects late events and results in abnormally elongated anaphase II spindles that abolish the linear order of nuclei in the ascus [70]. These observations suggest that higher levels of DDK and related kinase activities are important for the execution of meiotic recombination and chromosome segregation.…”