Abstract
Meiosis divides the chromosome number of the cell in half by having two rounds of chromosome segregation follow a single round of chromosome duplication. The first meiotic division is unique in that homologous pairs of sister chromatids segregate to opposite poles. Recent work in budding and fission yeast has shown that the cell cycle kinase, Cdc7-Dbf4, is required for many meiosis-specific chromosomal functions necessary for proper disjunction at meiosis I. This work reveals another role for Cdc7 in meiosis as a gene-specific regulator of the global transcription factor, Ndt80, which is required for exit from pachytene and entry into the meiotic divisions in budding yeast. Cdc7-Dbf4 promotes NDT80 transcription by relieving repression mediated by a complex of Sum1, Rfm1, and a histone deacetylase, Hst1. Sum1 exhibits meiosis-specific Cdc7-dependent phosphorylation, and mass spectrometry analysis reveals a dynamic and complex pattern of phosphorylation events, including four constitutive cyclin-dependent kinase (Cdk1) sites and 11 meiosis-specific Cdc7-Dbf4-dependent sites. Analysis of various phosphorylation site mutants suggests that Cdc7 functions with both Cdk1 and the meiosis-specific kinase Ime2 to control this critical transition point during meiosis.
SUPPLEMENTAL MATERIAL
Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.06032-11.
ACKNOWLEDGMENTS
We thank Huei-Mei Chen, Bruce Futcher, Ed Luk, Aaron Neiman, Jacqueline Segall, and Rolf Sternglanz for helpful discussions. Bruce Futcher, Aaron Neiman, and Rolf Sternglanz provided helpful comments on the manuscript. Michael Lichten, Laura Rusche, Jacqueline Segall, Rolf Sternglanz, and Edward Winter generously provided antibodies, strains, or plasmids. We are grateful to Chao Zhang and Kevan Shokat for PP1. Thanks go to Rachel Salatka for constructing the H310Y hst1 alleles.
This work was supported by NIH grants R01GM50717 and 5P01GM088297 to N.M.H. and HG3456 to S.P.G.