期刊
GENES & DEVELOPMENT
卷 22, 期 3, 页码 386-397出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1626408
关键词
meiotic recombination; cdc7; double-strand breaks; CDK; phosphorylation
资金
- Cancer Research UK Funding Source: Medline
- NIAID NIH HHS [R01 AI044009, AI44009] Funding Source: Medline
- NIGMS NIH HHS [GM64813, R01 GM064813, R01 GM050717, GM50717] Funding Source: Medline
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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