Matos Joao, Lipp Jesse J, Bogdanova Aliona, Guillot Sylvine, Okaz Elwy, Junqueira Magno, Shevchenko Andrej, Zachariae Wolfgang
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Cell. 2008 Nov 14;135(4):662-78. doi: 10.1016/j.cell.2008.10.026.
Meiosis differs from mitosis in that DNA replication is followed by the segregation of homologous chromosomes but not sister chromatids. This depends on the formation of interhomolog connections through crossover recombination and on the attachment of sister kinetochores to microtubules emanating from the same spindle pole. We show that in yeast, the Dbf4-dependent Cdc7 kinase (DDK) provides a link between premeiotic S phase, recombination, and monopolar attachment. Independently from its established role in initiating DNA replication, DDK promotes double-strand break formation, the first step of recombination, and the recruitment of the monopolin complex to kinetochores, which is essential for monopolar attachment. DDK regulates monopolin localization together with the polo-kinase Cdc5 bound to Spo13, probably through phosphorylation of the monopolin subunit Lrs4. Thus, activation of DDK both initiates DNA replication and commits meiotic cells to reductional chromosome segregation in the first division of meiosis.
减数分裂与有丝分裂的不同之处在于，DNA复制之后是同源染色体的分离，而非姐妹染色单体的分离。这依赖于通过交叉重组形成的同源染色体间连接，以及姐妹动粒与来自同一纺锤体极的微管的附着。我们发现，在酵母中，依赖Dbf4的Cdc7激酶（DDK）在减数分裂前S期、重组和单极附着之间提供了一种联系。DDK独立于其在启动DNA复制中已确立的作用，促进双链断裂的形成，即重组的第一步，并促进单极蛋白复合物募集到动粒，这对单极附着至关重要。DDK与结合在Spo13上的polo激酶Cdc5一起调节单极蛋白的定位，可能是通过磷酸化单极蛋白亚基Lrs4来实现。因此，DDK的激活既启动了DNA复制，又使减数分裂细胞在减数第一次分裂中进行减数染色体分离。
