Cloning and characterization of mouse Dhm2 cDNA, a functional homolog of budding yeast SEP1

We have isolated mouse Dhm2 cDNAs encoding a homolog of budding yeast SEP1, whose product is involved in many cellular processes including meiosis, cellular senescence, and telomere maintenance. The putative Dhm2 protein (Dhm2p), which consists of 1687 amino acids and whose molecular weight is 191,400, matches the size of Sep1p and shares extensive homology with Sep1p especially in their N-terminal regions. A multicopy plasmid containing of the Dhm2 cDNA complements the slow growth phenotype, sporulation defect, and DNA recombination defect caused by the sep1 mutation in yeast, indicating that Dhm2 is a functional homolog of SEP1. Since Dhm1, another SEP1 homolog we reported previously, only partially compensates for the sep1 mutation, we conclude that Dhm2 is a true homolog of SEP1. Northern analysis revealed that 5.8 kb mRNA corresponding to Dhm2 open reading frame is produced highly in testis. These results strongly suggest that Dhm2p participates in gametogenesis in mouse.