Basrai M A, Velculescu V E, Kinzler K W, Hieter P
Department of Molecular Biology & Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Mol Cell Biol. 1999 Oct;19(10):7041-9. doi: 10.1128/MCB.19.10.7041.
Analysis of global gene expression in Saccharomyces cerevisiae by the serial analysis of gene expression technique has permitted the identification of at least 302 previously unidentified transcripts from nonannotated open reading frames (NORFs). Transcription of one of these, NORF5/HUG1 (hydroxyurea and UV and gamma radiation induced), is induced by DNA damage, and this induction requires MEC1, a homolog of the ataxia telangiectasia mutated (ATM) gene. DNA damage-specific induction of HUG1, which is independent of the cell cycle stage, is due to the alleviation of repression by the Crt1p-Ssn6p-Tup1p complex. Overexpression of HUG1 is lethal in combination with a mec1 mutation in the presence of DNA damage or replication arrest, whereas a deletion of HUG1 rescues the lethality due to a mec1 null allele. HUG1 is the first example of a NORF with important biological functional properties and defines a novel component of the MEC1 checkpoint pathway.
通过基因表达序列分析技术对酿酒酵母中的全局基因表达进行分析，已鉴定出至少302个来自非注释开放阅读框（NORFs）的先前未鉴定的转录本。其中之一，NORF5/HUG1（羟基脲、紫外线和γ辐射诱导），其转录由DNA损伤诱导，且这种诱导需要MEC1，它是共济失调毛细血管扩张突变（ATM）基因的同源物。HUG1的DNA损伤特异性诱导独立于细胞周期阶段，这是由于Crt1p-Ssn6p-Tup1p复合物对其抑制作用的减轻。在存在DNA损伤或复制停滞的情况下，HUG1的过表达与mec1突变结合是致死的，而HUG1的缺失可挽救由于mec1无效等位基因导致的致死性。HUG1是具有重要生物学功能特性的NORF的首个实例，并定义了MEC1检查点途径的一个新组分。
