Tishkoff D X, Amin N S, Viars C S, Arden K C, Kolodner R D
Ludwig Institute for Cancer Research, Cancer Center, University of California School of Medicine at San Diego, La Jolla 92093, USA.
Cancer Res. 1998 Nov 15;58(22):5027-31.
The EXO1 gene was identified in Saccharomyces cerevisiae as a gene encoding an exonuclease that interacts with MSH2 and functions in mismatch repair and genetic recombination. To understand the role of EXO1 in higher eukaryotes, we identified the human EXO1 gene. The hEXO1 predicted amino acid sequence shares 26.6% identity with the S. cerevisiae EXO1 amino acid sequence. The human and S. cerevisiae proteins showed a similar ability to complement the mutator phenotype of S. cerevisiae rad27 mutants indicating that the two proteins are functionally similar. There appear to be two forms of hEXO1 that differ by the COOH-terminal 1 and 44 amino acids, respectively, and these appear to result from alternative RNA splicing. The hEXO1 gene consists of 14 exons and is transcribed to yield a 3-kb mRNA. Radiation hybrid and fluorescence in situ hybridization mapping studies indicate that the human gene is located at 1q42.2-qter. Northern blot analysis demonstrates that hEXO1 is expressed in high levels in testis; elevated expression was also observed in thymus and colon and to a lesser extent in small intestine, placenta, spleen, and ovary.
EXO1基因在酿酒酵母中被鉴定为一个编码核酸外切酶的基因，该核酸外切酶与MSH2相互作用并在错配修复和基因重组中发挥作用。为了了解EXO1在高等真核生物中的作用，我们鉴定了人类EXO1基因。hEXO1预测的氨基酸序列与酿酒酵母EXO1氨基酸序列的一致性为26.6%。人类和酿酒酵母的蛋白质在互补酿酒酵母rad27突变体的突变体表型方面表现出相似的能力，这表明这两种蛋白质在功能上相似。似乎有两种形式的hEXO1，它们分别在COOH末端相差1个和44个氨基酸，这似乎是由选择性RNA剪接导致的。hEXO1基因由14个外显子组成，转录产生一个3 kb的mRNA。辐射杂种和荧光原位杂交定位研究表明，人类基因位于1q42.2 - qter。Northern印迹分析表明，hEXO1在睾丸中高水平表达；在胸腺和结肠中也观察到表达升高，在小肠、胎盘、脾脏和卵巢中的表达程度较低。
