Cdc28-Clb5 (CDK-S) and Cdc7-Dbf4 (DDK) collaborate to initiate meiotic recombination in yeast.
S-phase cyclin-dependent kinase Cdc28-Clb5 (CDK-S) and Dbf4-dependent kinase Cdc7-Dbf4 (DDK) are highly conserved kinases well known for their roles in the initiation of DNA replication. CDK-S is also essential for initiation of meiotic recombination because it phosphorylates Ser30 of Mer2, a meiosis-specific double-strand break (DSB) protein. This work shows that the phosphorylation of Mer2 Ser30 by CDK-S primes Mer2 for subsequent phosphorylation by DDK on Ser29, creating a negatively charged "patch" necessary for DSB formation. CDK-S and DDK phosphorylation of Mer2 S30 and S29 can be bypassed by phosphomimetic amino acids, but break formation under these conditions is still dependent on DDK and CDK-S activity. Coordination between premeiotic S and DSB formation may be achieved by using CDK-S and DDK to initiate both processes. Many other proteins important for replication, recombination, repair, and chromosome segregation contain combination DDK/CDK sites, raising the possibility that this is a common regulatory mechanism.
Wan
Lihong
L
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York 11794, USA.
Niu
Hengyao
H
Futcher
Bruce
B
Zhang
Chao
C
Shokat
Kevan M
KM
Boulton
Simon J
SJ
Hollingsworth
Nancy M
NM
D017489:CDC28 Protein Kinase, S cerevisiae / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D019926:Cyclin B / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology; D008540:Meiosis / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011995:Recombination, Genetic / Q000235:genetics / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*
C076558:CLB5 protein, S cerevisiae; D018797:Cell Cycle Proteins; D019926:Cyclin B; C088096:Dbf4 protein, S cerevisiae; C071054:REC107 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C489404:CDC7 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D017489:CDC28 Protein Kinase, S cerevisiae