Zhao X, Muller E G, Rothstein R
Department of Genetics and Development, Columbia University, College of Physicians and Surgeons, New York, New York 10032-2704, USA.
Mol Cell. 1998 Sep;2(3):329-40. doi: 10.1016/s1097-2765(00)80277-4.
In Saccharomyces cerevisiae, MEC1 and RAD53 are essential for cell growth and checkpoint function. Their essential role in growth can be bypassed by deletion of a novel gene, SML1, which functions after several genes whose overexpression also suppresses mec1 inviability. In addition, sml1 affects various cellular processes analogous to overproducing the large subunit of ribonucleotide reductase, RNR1. These include effects on mitochondrial biogenesis, on the DNA damage response, and on cell growth. Consistent with these observations, the levels of dNTP pools in sml1 delta strains are increased compared to wild-type. This effect is not due to an increase in RNR transcription. Finally, both in vivo and in vitro experiments show that Sml1 binds to Rnr1. We propose that Sml1 inhibits dNTP synthesis posttranslationally by binding directly to Rnr1 and that Mec1 and Rad53 are required to relieve this inhibition.
在酿酒酵母中，MEC1和RAD53对细胞生长和检查点功能至关重要。通过缺失一个新基因SML1，可以绕过它们在生长中的重要作用，SML1在几个基因之后发挥作用，这些基因的过表达也能抑制mec1的致死性。此外，sml1影响各种细胞过程，类似于过量产生核糖核苷酸还原酶的大亚基RNR1。这些影响包括对线粒体生物发生、DNA损伤反应和细胞生长的影响。与这些观察结果一致，与野生型相比，sml1缺失菌株中的dNTP库水平有所增加。这种效应不是由于RNR转录增加所致。最后，体内和体外实验均表明Sml1与Rnr1结合。我们提出，Sml1通过直接与Rnr1结合在翻译后抑制dNTP合成，并且Mec1和Rad53是解除这种抑制所必需的。
