Xu E Y, Kim S, Replogle K, Rine J, Rivier D H
Department of Cell and Structural Biology, University of Illinois, Urbana, Illinois 61801, USA.
Genetics. 1999 Sep;153(1):13-23. doi: 10.1093/genetics/153.1.13.
In Saccharomyces cerevisiae, chromatin-mediated silencing inactivates transcription of the genes at the HML and HMR cryptic mating-type loci and genes near telomeres. Mutations in the Rap1p and Abf1p binding sites of the HMR-E silencer (HMRa-e**) result in a loss of silencing at HMR. We characterized a collection of 15 mutations that restore the alpha-mating phenotype to MATalpha HMRa-e** strains. These mutations defined three complementation groups, two new groups and one group that corresponded to the previously identified SAS2 gene. We cloned the genes that complemented members of the new groups and identified two previously uncharacterized genes, which we named SAS4 and SAS5. Neither SAS4 nor SAS5 was required for viability. Null alleles of SAS4 and SAS5 restored SIR4-dependent silencing at HMR, establishing that each is a regulator of silencing. Null alleles of SAS4 and SAS5 bypassed the role of the Abf1p binding site of the HMR-E silencer but not the role of the ACS or Rap1p binding site. Previous analysis indicated that SAS2 is homologous to a human gene that is a site of recurring translocations involved in acute myeloid leukemia. Similarly, SAS5 is a member of a gene family that included two human genes that are the sites of recurring translocations involved in acute myeloid leukemia.
在酿酒酵母中，染色质介导的沉默作用会使位于HML和HMR隐蔽交配型位点以及端粒附近的基因的转录失活。HMR-E沉默子（HMRa-e**）的Rap1p和Abf1p结合位点发生突变会导致HMR处的沉默作用丧失。我们对一组15个突变进行了表征，这些突变可使MATα HMRa-e**菌株恢复α交配表型。这些突变定义了三个互补组，两个新组和一个与先前鉴定的SAS2基因相对应的组。我们克隆了与新组成员互补的基因，并鉴定出两个以前未表征的基因，我们将其命名为SAS4和SAS5。SAS4和SAS5对于细胞存活都不是必需的。SAS4和SAS5的无效等位基因恢复了HMR处依赖SIR4的沉默作用，表明它们各自都是沉默作用的调节因子。SAS4和SAS5的无效等位基因绕过了HMR-E沉默子的Abf1p结合位点的作用，但没有绕过ACS或Rap1p结合位点的作用。先前的分析表明，SAS2与一个人类基因同源，该人类基因是急性髓性白血病中反复发生易位的位点。同样，SAS5是一个基因家族的成员，该家族包括两个人类基因，它们是急性髓性白血病中反复发生易位的位点。
