Sanchez Y, Desany B A, Jones W J, Liu Q, Wang B, Elledge S J
Verna and Mars McLean Department of Biochemistry, Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Science. 1996 Jan 19;271(5247):357-60. doi: 10.1126/science.271.5247.357.
Mutants of the Saccharomyces cerevisiae ataxia telangiectasia mutated (ATM) homolog MEC1/SAD3/ESR1 were identified that could live only if the RAD53/SAD1 checkpoint kinase was overproduced. MEC1 and a structurally related gene, TEL1, have overlapping functions in response to DNA damage and replication blocks that in mutants can be provided by overproduction of RAD53. Both MEC1 and TEL1 were found to control phosphorylation of Rad53p in response to DNA damage. These results indicate that RAD53 is a signal transducer in the DNA damage and replication checkpoint pathways and functions downstream of two members of the ATM lipid kinase family. Because several members of this pathway are conserved among eukaryotes, it is likely that a RAD53-related kinase will function downstream of the human ATM gene product and play an important role in the mammalian response to DNA damage.
酿酒酵母共济失调毛细血管扩张症突变（ATM）同源物MEC1/SAD3/ESR1的突变体被鉴定出来，这些突变体只有在RAD53/SAD1检查点激酶过量表达时才能存活。MEC1和一个结构相关基因TEL1在对DNA损伤和复制阻滞的反应中具有重叠功能，在突变体中，RAD53的过量表达可以提供这些功能。研究发现，MEC1和TEL1在响应DNA损伤时都能控制Rad53p的磷酸化。这些结果表明，RAD53是DNA损伤和复制检查点途径中的信号转导器，在ATM脂质激酶家族的两个成员下游发挥作用。由于该途径的几个成员在真核生物中是保守的，因此与RAD53相关的激酶很可能在人类ATM基因产物下游发挥作用，并在哺乳动物对DNA损伤的反应中起重要作用。
