Fedorov D V, Koval'tsova S V, Peshekhonov V T, Korolev V G
Genetika. 2010 Jun;46(6):750-7.
The yeast genes IXR1 and HMO1 encode proteins belonging to the family of chromatin nonhistone proteins, which are able to recognize and bind to irregular DNA structures. The full deletion of gene IXR1 leads to an increase in cell resistance to the lethal action of UV light, gamma-rays, and MMS, increases spontaneous mutagenesis and significantlly decreases the level of UV-induced mutations. It was earlier demonstrated in our works that the hmo 1 mutation renders cells sensitive to the lethal action of cisplatin and virtually does not affect the sensitivity to UV light. Characteristically, the rates of spontaneous and UV-induced mutagenesis in the mutant are increased. Epistatic analysis of the double mutation hmo 1 ixr1 demonstrated that the interaction of these genes in relation to the lethal effect of cisplatin and UV light, as well as UV-induced mutagenesis, is additive. This suggests that the products of genes HMO1 and IXR1 participate in different repair pathways. The ixr1 mutation significantly increases the rate of spontaneous mutagenesis mediated by replication errors, whereas mutation hmo 1 increases the rate of repair mutagenesis. In wild-type cells, the level of spontaneous mutagenesis was nearly one order of magnitude lower than that obtained in cells of the double mutant. Consequently, the combined activity of the Hmo 1 and the Ixr1 proteins provides efficient correction of both repair and replication errors.
酵母基因IXR1和HMO1编码属于染色质非组蛋白家族的蛋白质，这些蛋白质能够识别并结合不规则的DNA结构。基因IXR1的完全缺失导致细胞对紫外线、γ射线和甲基磺酸甲酯的致死作用的抗性增加，增加自发诱变率，并显著降低紫外线诱导的突变水平。我们之前的研究表明，hmo 1突变使细胞对顺铂的致死作用敏感，而实际上不影响对紫外线的敏感性。值得注意的是，突变体中自发诱变和紫外线诱导诱变的速率都增加了。对双突变hmo 1 ixr1的上位性分析表明，这些基因在顺铂和紫外线的致死效应以及紫外线诱导诱变方面的相互作用是累加的。这表明基因HMO1和IXR1的产物参与不同的修复途径。ixr1突变显著增加了由复制错误介导的自发诱变率，而hmo 1突变增加了修复诱变率。在野生型细胞中，自发诱变水平比双突变体细胞中的水平低近一个数量级。因此，Hmo 1和Ixr1蛋白的联合活性可有效校正修复和复制错误。
