Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C/Doctor Aiguader 88, Barcelona 08003, Spain.
EMBO Rep. 2011 Jan;12(1):84-9. doi: 10.1038/embor.2010.187. Epub 2010 Dec 3.
When DNA replication is challenged cells activate a DNA synthesis checkpoint, blocking cell cycle progression until they are able to overcome the replication defects. In fission yeast, Cds1 is the effector kinase of this checkpoint, inhibiting M-phase entry, stabilizing stalled replication forks and triggering transcriptional activation of S-phase genes. The molecular basis of this last effect is largely unknown. The Mlu1 binding factor (MBF) complex controls the transcription of S-phase genes. We purified novel interactors of the MBF complex and identified the repressor Yox1. When the DNA synthesis checkpoint is activated, Yox1 is phosphorylated, which abrogates its binding to MBF. MBF-dependent transcription therefore remains active until cells are able to overcome this challenge.
当 DNA 复制受到挑战时,细胞会激活 DNA 合成检查点,阻止细胞周期进程,直到它们能够克服复制缺陷。在裂殖酵母中,Cds1 是该检查点的效应激酶,它抑制 M 期进入,稳定停滞的复制叉,并触发 S 期基因的转录激活。最后这个效应的分子基础在很大程度上是未知的。Mlu1 结合因子 (MBF) 复合物控制 S 期基因的转录。我们纯化了 MBF 复合物的新相互作用蛋白,并鉴定出了抑制子 Yox1。当 DNA 合成检查点被激活时,Yox1 被磷酸化,从而使其与 MBF 的结合被解除。因此,MBF 依赖性转录在细胞能够克服这一挑战之前仍然保持活跃。