Human and mouse RAD17 genes: identification, localization, genomic structure and histological expression pattern in normal testis and seminoma

Recently, the human orthologue to the cell cycle checkpoint genes rad17 (Sc hizosaccharomyces pombe) and RAD24 (Saccharomyces cerevisiae), called HRAD1 7, has been isolated and localized to chromosome 4. Independently, we have isolated the HRAD17 transcript and mapped it to chromosome 5q13 between the CCNB1 and BTF2p44cen genes. Furthermore, we have identified the complete e xon-intron structure of HRAD17. The gene is organized into 14 exons, the tr anslation initiation site lies within exon 2, and the stop codon within exo n 14. TWO further HRAD17 pseudogenes, HRAD17P1 and HRAD17P2, were identifie d on chromosomes 7p21 and 13q14.3, respectively, encompassing exons 3-14 an d bearing 84% and 93% homology, respectively. Additionally, we have isolate d the coding region of the mouse orthologue, Mrad17, and mapped it on chrom osome 13 between Ccnb1 and Btf2p44, the same two genes between which it map s in human. The predicted Mrad17 polypeptide encompasses 687 amino acids an d shows 89% similarity to HRAD17. Both genes are most highly expressed in t estis compared to all other tissues, as shown by Northern blot hybridizatio n. Histological studies, based on in situ hybridization with radioactively labeled antisense HRAD17 riboprobes, showed a strong expression within the germinal epithelium of the seminiferous tubuli in normal testis whereas in testicular tumors (seminomas) only weak, diffuse signals were seen. In ligh t of the known function of the yeast orthologue at meiotic and mitotic chec kpoints, as well as the strong expression in testis and weak expression in seminomas, we suggest a putative involvement of HRAD17 in testicular tumori genesis.