Identification of a human gene encoding a homologue of Saccharomyces cerevisiae EXO1, an exonuclease implicated in mismatch repair and recombination.

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.