Role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae
Role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae
复制标题
DOI：
10.1016/j.mrrev.2003.06.018
复制
发表时间：
2003-11-01
影响因子：
5.3
通讯作者：
Henriques, JAP
中科院分区：
文献类型：
--
作者：
Brendel, M;Bonatto, D;Henriques, JAP
用于治疗牛皮癣和白癜风等皮肤病的光活化补骨脂素会导致DNA损伤，修复DNA损伤可能导致突变，从而增加患皮肤癌的风险。我们选择简单的真核生物酿酒酵母菌来研究这种类型DNA损伤的细胞遗传修复机制，并研究这种修复的遗传后果。对光活化补骨脂素敏感的酵母突变体（pso突变体）的遗传研究表明，它们分布在10个不同的位点上。克隆和分子表征使它们可以分为三个功能类别：(I)最大的一类包括七个PSO基因，这些基因通常或专门参与易出错的DNA修复，从而影响诱导突变和重组；（II）一个PSO基因代表无错误切除修复，（III）两个PSO基因编码的蛋白质不影响DNA修复，但与核酸代谢无关的生理过程。在参与诱变的7个DNA修复基因中，有3个PSO位点[PSO1/REV3， PSO8/RAD6， PSO9/MEC3]是已知修复基因的等位基因，而PSO2/SNM1， PSO3/RNR4和PSO4/PRP19是酿酒酵母中参与DNA修复和核酸代谢的新基因。基因PSO2编码一种修复链间交联（ICL）所必需的蛋白质，这种蛋白质是由多种双功能和多功能诱变剂在DNA中产生的，它似乎对人类的类似修复功能也很重要。硅分析预测Pso2p/Snm1p在去除作为修复中间体产生的发夹时可能具有核内溶活性。pso3/rnr4突变体中缺乏诱导突变表明该核糖核苷酸亚基的重要作用。还原酶（RNR）在易出错修复中调控翻译聚合酶zeta。Prp19p/Pso4p通过剪接含内含子的修复基因的前mrna影响DNA修复效率，但也可能在影响DNA修复能力的核支架稳定性中发挥作用。第七个基因PSO10控制诱导诱变的一个未知步骤，目前尚未克隆。两个基因PSO6/ERG3和PSO7/COX11分别负责膜的结构元件和功能呼吸链（RC），因此它们的功能间接影响对光激活补骨脂素的敏感性。(C) 2003 Elsevier B.V.版权所有
Photoactivated psoralens used in treatment of skin diseases like Psoriasis and Vitiligo cause DNA damage, the repair of which may lead to mutations and thus to higher risk to have skin cancer. The simple eukaryote Saccharomyces cerevisiae was chosen to investigate the cells' genetic endowment with repair mechanisms for this type of DNA damage and to study the genetic consequences of such repair. Genetic studies on yeast mutants sensitive to photoactivated psoralens, named pso mutants, showed their allocation to 10 distinct loci. Cloning and molecular characterization allowed their grouping into three functional classes: (I) the largest group comprises seven PSO genes that are either generally or specifically involved in error-prone DNA repair and thus affect induced mutability and recombination; (II) one PSO gene that represents error-free excision repair, and (III) two PSO genes encoding proteins not influencing DNA repair but physiological processes unrelated to nucleic acid metabolism. Of the seven DNA repair genes involved in induced mutagenesis three PSO loci [PSO1/REV3, PSO8/RAD6, PSO9/MEC3] were allelic to already known repair genes, whereas three, PSO2/SNM1, PSO3/RNR4, and PSO4/PRP19 represent new genes involved in DNA repair and nucleic acid metabolism in S. cerevisiae. Gene PSO2 encodes a protein indispensable for repair of interstrand cross-link (ICL) that are produced in DNA by a variety of bi- and polyfunctional mutagens and that appears to be important for a likewise repair function in humans as well. In silico analysis predicts a putative endonucleolytic activity for Pso2p/Snm1p in removing hairpins generated as repair intermediates. The absence of induced mutation in pso3/rnr4 mutants indicates an important role of this subunit of ribonucleotide. reductase (RNR) in regulation of translesion polymerase zeta in error-prone repair. Prp19p/Pso4p influences efficiency of DNA repair via splicing of pre-mRNAs of intron-containing repair genes but also may function in the stability of the nuclear scaffold that might influence DNA repair capacity. The seventh gene, PSO10 which controls an unknown step in induced mutagenesis is not yet cloned. Two genes, PSO6/ERG3 and PSO7/COX11, are responsible for structural elements of the membrane and for a functional respiratory chain (RC), respectively, and their function thus indirectly influences sensitivity to photoactivated psoralens. (C) 2003 Elsevier B.V. All rights reserved.