Valentin Guillaume, Schwob Etienne, Della Seta Flavio
Institute of Molecular Genetics and Université Montpellier II, CNRS UMR5535-1919, Route de Mende, F-34293 Montpellier Cedex 5, France.
J Biol Chem. 2006 Feb 3;281(5):2828-34. doi: 10.1074/jbc.M510626200. Epub 2005 Nov 30.
The Dbf4-dependent Cdc7 kinase (DDK) is essential for chromosome duplication in all eukaryotes, but was proposed to be dispensable for yeast pre-meiotic DNA replication. This discrepancy led us to investigate the role of the unstable Cdc7-regulatory protein Dbf4 in meiosis. We show that, when Dbf4 is depleted at the time of meiotic induction, cells enter the meiotic program but do not replicate their chromosomes. Surprisingly when Dbf4 is depleted after the initiation of DNA synthesis, S phase goes to completion, but most cells arrest before anaphase I. Deletion of the cohesin Rec8 suppresses this phenotype, suggesting a distinct role of DDK for meiotic chromosome segregation. As after Cdc5 depletion, a fraction of cells undergo a single equational division suggesting a failure to mono-orient sister kinetochores. Our results demonstrate that Dbf4 is essential for DNA replication during meiosis like in vegetative cells and provide evidence for an additional role in setting up the reductional division of meiosis I.
依赖Dbf4的Cdc7激酶(DDK)对于所有真核生物的染色体复制至关重要,但曾有人提出它对于酵母减数分裂前的DNA复制是可有可无的。这种差异促使我们研究不稳定的Cdc7调节蛋白Dbf4在减数分裂中的作用。我们发现,当在减数分裂诱导时Dbf4被耗尽,细胞进入减数分裂程序但不复制其染色体。令人惊讶的是,当在DNA合成起始后Dbf4被耗尽时,S期完成,但大多数细胞在减数第一次分裂后期之前停滞。黏连蛋白Rec8的缺失抑制了这种表型,表明DDK在减数分裂染色体分离中具有独特作用。就像在Cdc5被耗尽后一样,一部分细胞经历一次均等分裂,这表明未能使姐妹动粒单极定向。我们的结果表明,Dbf4对于减数分裂期间的DNA复制就像在营养细胞中一样至关重要,并为其在建立减数第一次分裂的减数分裂中的额外作用提供了证据。