Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
Dev Cell. 2010 Mar 16;18(3):397-409. doi: 10.1016/j.devcel.2010.01.014.
During meiosis, two rounds of chromosome segregation after a single round of DNA replication produce haploid gametes from diploid precursors. At meiosis I, maternal and paternal kinetochores are pulled toward opposite poles, and chiasmata holding bivalent chromosomes together are resolved by cleavage of cohesin's alpha-kleisin subunit (Rec8) along chromosome arms. This creates dyad chromosomes containing a pair of chromatids joined solely by cohesin at centromeres that had resisted cleavage. The discovery that centromeric Rec8 is protected from separase during meiosis I by shugoshin/MEI-S332 proteins that bind PP2A phosphatase suggests that phosphorylation either of separase or cohesin may be necessary for Rec8 cleavage. We show here that multiple phosphorylation sites within Rec8 as well as two different kinases, casein kinase 1delta/epsilon (CK1delta/epsilon) and Dbf4-dependent Cdc7 kinase (DDK), are required for Rec8 cleavage and meiosis I nuclear division. Rec8 with phosphomimetic mutations is no longer protected from separase at centromeres and is cleaved even when the two kinases are inhibited. Our data suggest that PP2A protects centromeric cohesion by opposing CK1delta/epsilon- and DDK-dependent phosphorylation of Rec8.
在减数分裂过程中，经过一轮 DNA 复制，会发生两轮染色体分离，从而从二倍体前体中产生单倍体配子。在减数分裂 I 期，母源和父源动粒向相反的两极牵拉，并且联会的二价染色体通过沿着染色体臂切割黏连蛋白的α- kleisin 亚基（Rec8）而分开。这就产生了包含一对仅在着丝粒处由黏连蛋白连接的染色单体的二分体染色体，而这些着丝粒处的黏连蛋白抵抗了切割。发现 Rec8 上的着丝粒结合的 Shugoshin/MEI-S332 蛋白可以保护减数分裂 I 期的中心体 Rec8 免受分离酶的作用，这表明分离酶或黏连蛋白的磷酸化可能是 Rec8 切割所必需的。我们在这里表明，Rec8 中的多个磷酸化位点以及两种不同的激酶，酪蛋白激酶 1 delta/epsilon（CK1delta/epsilon）和 Dbf4 依赖性 Cdc7 激酶（DDK），对于 Rec8 切割和减数分裂 I 核分裂是必需的。具有磷酸模拟突变的 Rec8 不再受到中心体分离酶的保护，即使两种激酶被抑制，它也会被切割。我们的数据表明，PP2A 通过拮抗 CK1delta/epsilon 和 DDK 依赖性的 Rec8 磷酸化来保护着丝粒的黏合。
