Cdc28–Clb5 (CDK-S) and Cdc7–Dbf4 (DDK) collaborate to initiate meiotic recombination in yeast
- Lihong Wan1,
- Hengyao Niu1,
- Bruce Futcher2,
- Chao Zhang3,
- Kevan M. Shokat3,
- Simon J. Boulton4, and
- Nancy M. Hollingsworth1,5
- 1 Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York 11794, USA;
- 2 Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794, USA;
- 3 Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, California 94158, USA;
- 4 London Research Institute, Clare Hall Laboratories, South Mims, Herts EN6 3LD, United Kingdom
Abstract
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.
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Footnotes
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↵5 Corresponding author.
↵5 E-MAIL nhollin{at}ms.cc.sunysb.edu; FAX (631) 632-8575.
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Supplemental material is available at http://www.genesdev.org.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1626408
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- Received October 16, 2007.
- Accepted December 7, 2007.
- Copyright © 2008, Cold Spring Harbor Laboratory Press
