Program in Molecular and Computational Biology, University of Southern California , Los Angeles, CA 90089-2910 , USA.
Biol Open. 2013 Jun 11;2(7):728-38. doi: 10.1242/bio.20135173. Print 2013 Jul 15.
The DDK complex is a conserved kinase complex, consisting of a catalytic subunit, Hsk1 (Cdc7), and its regulatory subunit Dfp1 (Dbf4). This kinase is essential for DNA replication. In this work, we show that dfp1-r35, which truncates the Dfp1 C-terminus zinc finger, causes severe meiotic defects, including reduced spore viability, reduced formation of programmed double strand breaks, altered expression of meiotic genes, and disrupted chromosome segregation. There is a high frequency of dyad formation. Mutants are also defective in the phosphorylation and degradation of the meiotic cohesion, Rec8, resulting in a failure to proceed through the MII division. These defects are more pronounced in a haploid meiosis model than in a normal diploid meiosis. Thus, several critical meiotic functions are linked specifically to the C-terminus of Dfp1, which may target specific substrates for phosphorylation by Hsk1.
DDK 复合物是一个保守的激酶复合物,由一个催化亚基 Hsk1(Cdc7)及其调节亚基 Dfp1(Dbf4)组成。这种激酶对 DNA 复制至关重要。在这项工作中,我们表明,截断 Dfp1 C 端锌指的 dfp1-r35 导致严重的减数分裂缺陷,包括孢子活力降低、程序性双链断裂形成减少、减数分裂基因表达改变以及染色体分离紊乱。二联体的形成频率很高。突变体还存在减数分裂黏合蛋白 Rec8 的磷酸化和降解缺陷,导致无法进行 MII 分裂。在单倍体减数分裂模型中,这些缺陷比在正常二倍体减数分裂中更为明显。因此,几个关键的减数分裂功能与 Dfp1 的 C 端特异性相关,这可能将特定的底物靶向 Hsk1 的磷酸化。