Lindgren A, Bungard D, Pierce M, Xie J, Vershon A, Winter E
Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
EMBO J. 2000 Dec 1;19(23):6489-97. doi: 10.1093/emboj/19.23.6489.
Saccharomyces cerevisiae mutants that fail to complete meiotic recombination are blocked by the RAD17/RAD24/MEC1 checkpoint signaling pathway in pachytene when early sporulation genes are expressed. Middle genes are not activated in checkpoint-arrested cells because the Ndt80 transcription factor is inhibited. We find that the pachytene checkpoint requires Sum1, a transcriptional repressor that recognizes a subset of Ndt80-binding sites. Mutants lacking Sum1 or Rad17 partially bypass the block to the nuclear divisions but do not form spores, while mutants lacking both Sum1 and Rad17 completely bypass the block and form morphologically normal spores. The level of Sum1 protein decreases as middle genes are expressed, and this decrease is blocked in checkpoint-arrested cells. These data suggest that Sum1 levels are regulated by the checkpoint and that progression of the meiotic divisions and spore differentiation can be differentially controlled by competition of the Sum1 repressor and Ndt80 activator for occupancy at key middle promoters.
当早期孢子形成基因表达时,未能完成减数分裂重组的酿酒酵母突变体在粗线期被RAD17/RAD24/MEC1检查点信号通路阻断。中期基因在检查点阻滞的细胞中不被激活,因为Ndt80转录因子受到抑制。我们发现粗线期检查点需要Sum1,一种识别Ndt80结合位点子集的转录抑制因子。缺乏Sum1或Rad17的突变体部分绕过了对核分裂的阻滞,但不形成孢子,而同时缺乏Sum1和Rad17的突变体完全绕过了阻滞并形成形态正常的孢子。随着中期基因的表达,Sum1蛋白水平下降,而这种下降在检查点阻滞的细胞中被阻断。这些数据表明Sum1水平受检查点调控,减数分裂和孢子分化的进程可通过Sum1抑制因子和Ndt80激活因子在关键中期启动子处占据的竞争而受到差异控制。