Xiao W, Singh K K, Chen B, Samson L
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115.
Mol Cell Biol. 1993 Dec;13(12):7213-21. doi: 10.1128/mcb.13.12.7213-7221.1993.
The Saccharomyces cerevisiae MAG gene encodes a 3-methyladenine DNA glycosylase that protects cells from killing by alkylating agents. MAG mRNA levels are induced not only by alkylating agents but also by DNA-damaging agents that do not produce alkylated DNA. We constructed a MAG-lacZ gene fusion to help identify the cis-acting promoter elements involved in regulating MAG expression. Deletion analysis defined the presence of one upstream activating sequence and one upstream repressing sequence (URS) and suggested the presence of a second URS. One of the MAG URS elements matches a decamer consensus sequence present in the promoters of 11 other S. cerevisiae DNA repair and metabolism genes, including the MGT1 gene, which encodes an O6-methylguanine DNA repair methyltransferase. Two proteins of 26 and 39 kDa bind specifically to the MAG and MGT1 URS elements. We suggest that the URS-binding proteins may play an important role in the coordinate regulation of these S. cerevisiae DNA repair genes.
酿酒酵母MAG基因编码一种3 - 甲基腺嘌呤DNA糖基化酶,可保护细胞免受烷基化剂的杀伤。MAG mRNA水平不仅受烷基化剂诱导,还受不会产生烷基化DNA的DNA损伤剂诱导。我们构建了一个MAG - lacZ基因融合体,以帮助鉴定参与调节MAG表达的顺式作用启动子元件。缺失分析确定了一个上游激活序列和一个上游抑制序列(URS)的存在,并提示存在第二个URS。MAG的一个URS元件与其他11个酿酒酵母DNA修复和代谢基因(包括编码O6 - 甲基鸟嘌呤DNA修复甲基转移酶的MGT1基因)启动子中存在的一个十聚体共有序列相匹配。两种分别为26 kDa和39 kDa的蛋白质特异性结合MAG和MGT1的URS元件。我们认为,URS结合蛋白可能在这些酿酒酵母DNA修复基因的协同调节中发挥重要作用。