Cell cycle checkpoint control

在减数分裂期间，由DNA双链断裂（DSB）引发的高水平重组仅发生在DNA复制之后。然而，DSB的形成如何与DNA复制相结合尚不清楚。我们研究了几种DNA复制蛋白在裂殖酵母的这种耦合中的作用，现在表明，核糖核苷酸还原酶（RNR），脱氧核糖核苷酸合成的限速酶和DNA合成抑制剂羟基脲（HU）的目标，是间接需要DSB形成连接到DNA复制。然而，在DNA复制检查点蛋白Rad1p、Rad3p、Rad9p、Rad17p、Rad26p、Hus1p或Cdslp的功能受损的细胞中，在不存在或存在HU的情况下，DSB形成以相似的频率发生。HU处理的突变细胞中的DSB发生在正常位点，并与重组有关。此外，Cdc2p显然不参与这一过程。我们认为减数分裂S期的序列和重组的启动是由DNA复制检查点蛋白协调的。

During meiosis, high levels of recombination initiated by DNA double-strand breaks (DSBs) occur only after DNA replication. How DSB formation is coupled to DNA replication is unknown, however. We examined several DNA replication proteins for a role in this coupling in Schizosaccharomyces pombe and now show that ribonucleotide reductase (RNR), the rate-limiting enzyme of deoxyribonucleotide synthesis and the target of the DNA synthesis inhibitor hydroxyurea (HU), is indirectly required for DSB formation linked to DNA replication. In cells in which the function of the DNA replication checkpoint proteins Rad1p, Rad3p, Rad9p, Rad17p, Rad26p, Hus1p, or Cdslp was compromised, however, DSB formation occurred at similar frequencies in the absence or presence of HU. The DSBs in the HU-treated mutant cells occurred at normal sites and were associated with recombination. In addition, Cdc2p is apparently not involved in this process. We propose that the sequence of meiotic S phase and initiation of recombination is coordinated by DNA replication checkpoint proteins.