S-PHASE FEEDBACK-CONTROL IN BUDDING YEAST INDEPENDENT OF TYROSINE PHOSPHORYLATION OF P34CDC28
S-PHASE FEEDBACK-CONTROL IN BUDDING YEAST INDEPENDENT OF TYROSINE PHOSPHORYLATION OF P34CDC28
复制标题
DOI：
10.1038/355365a0
复制
发表时间：
1992-01-23
期刊：
影响因子：
64.8
通讯作者：
MURRAY, AW
中科院分区：
文献类型：
--
作者：
SORGER, PK;MURRAY, AW
在体细胞中，进入有丝分裂取决于DNA合成的完成。这种依赖性是由S期反馈控制建立的，当存在受损或未复制的DNA时，S期反馈控制会阻止细胞分裂1。 在裂殖酵母裂殖酵母中，干扰p34 cdc 2（成熟促进因子的蛋白激酶亚基）酪氨酸15（Y15）磷酸化的突变加速进入有丝分裂并消除未复制DNA将细胞阻滞在G2期的能力（参考文献2）。由于p34 cdc 2的酪氨酸磷酸化在S. p34 cdc 2-Y15磷酸化的调节可能是介导S期反馈控制和调节有丝分裂起始的普遍机制7，8。 我们已经调查了这些现象中的芽殖酵母酿酒酵母。我们在这里报告，CDC 28基因产物（S。在一些实施方案中，在S期期间，cdc 2的酿酒酵母同源物）在等同酪氨酸（Y19）上磷酸化，但是阻止酪氨酸磷酸化的突变不会导致过早的有丝分裂，并且不会消除反馈控制。因此，我们已经证明了一种不涉及p34酪氨酸磷酸化的机制，通过这种机制，细胞在未复制或受损DNA的存在下阻止其分裂。我们推测这一机制可能不涉及p34催化活性的失活。
IN somatic cells, entry into mitosis depends on the completion of DNA synthesis. This dependency is established by S-phase feedback controls that arrest cell division when damaged or unreplicated DNA is present 1. In the fission yeast Schizosaccharomyces pombe, mutations that interfere with the phosphorylation of tyrosine 15 (Y15) of p34cdc2,the protein kinase subunit of maturation promoting factor, accelerate the entry into mitosis and abolish the ability of unreplicated DNA to arrest cells in G2 (ref. 2). Because the tyrosine phosphorylation of p34cdc2 is conserved in S. pombe 3, Xenopus 4, chicken 5 and human 6 cells, the regulation of p34cdc2-Y15 phosphorylation could be a universal mechanism mediating the S-phase feedback control and regulating the initiation of Mitosis 7,8. We have investigated these phenomena in the budding yeast Saccharomyces cerevisiae. We report here that the CDC28 gene product (the S. cerevisiae homologue of cdc2) is phosphorylated on the equivalent tyrosine (Y19) during S phase but that mutations that prevent tyrosine phosphorylation do not lead to premature mitosis and do not abolish feedback controls. We have therefore demonstrated a mechanism that does not involve tyrosine phosphorylation of p34 by which cells arrest their division in response to the presence of unreplicated or damaged DNA. We speculate that this mechanism may not involve the inactivation of p34 catalytic activity.