Watson Adam, Mata Juan, Bähler Jürg, Carr Anthony, Humphrey Tim
Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, United Kingdom.
Mol Biol Cell. 2004 Feb;15(2):851-60. doi: 10.1091/mbc.e03-08-0569. Epub 2003 Dec 10.
A coordinated transcriptional response to DNA-damaging agents is required to maintain genome stability. We have examined the global gene expression responses of the fission yeast Schizosaccharomyces pombe to ionizing radiation (IR) by using DNA microarrays. We identified approximately 200 genes whose transcript levels were significantly altered at least twofold in response to 500 Gy of gamma IR in a temporally defined manner. The majority of induced genes were core environmental stress response genes, whereas the remaining genes define a transcriptional response to DNA damage in fission yeast. Surprisingly, few DNA repair and checkpoint genes were transcriptionally modulated in response to IR. We define a role for the stress-activated mitogen-activated protein kinase Sty1/Spc1 and the DNA damage checkpoint kinase Rad3 in regulating core environmental stress response genes and IR-specific response genes, both independently and in concert. These findings suggest a complex network of regulatory pathways coordinate gene expression responses to IR in eukaryotes.
为维持基因组稳定性，需要对DNA损伤剂产生协调的转录反应。我们通过使用DNA微阵列研究了裂殖酵母粟酒裂殖酵母对电离辐射（IR）的全局基因表达反应。我们鉴定出约200个基因，其转录水平在受到500 Gy的γ射线照射后，以时间定义的方式至少显著改变了两倍。大多数诱导基因是核心环境应激反应基因，而其余基因则定义了裂殖酵母中对DNA损伤的转录反应。令人惊讶的是，很少有DNA修复和检查点基因在转录水平上受到IR的调节。我们确定了应激激活的丝裂原活化蛋白激酶Sty1/Spc1和DNA损伤检查点激酶Rad3在独立和协同调节核心环境应激反应基因和IR特异性反应基因中的作用。这些发现表明，在真核生物中，一个复杂的调控途径网络协调了对IR的基因表达反应。
