MOLECULAR-CLONING AND STRUCTURAL-ANALYSIS OF MOUSE GENE AND PSEUDOGENES FOR PROLIFERATING CELL NUCLEAR ANTIGEN

We have isolated clones containing the entire mouse proliferating cell nuclear antigen (PCNA) gene of 3890 bp and flanking sequences using a rat PCNA cDNA as a probe. The mouse gene has 6 exons whose sequences and junction points of exons with introns are extensively homologous to the human gene while sizes and nucleotide sequences of introns are much less conserved than exons. By a transient expression assay of chloramphenicol acetyltransferase, the promoter of this gene is localized within 200 bp upstream of the transcription initiation site. We have also isolated two processed pseudogenes. Homology between the first one (psi-PCNA-I) and the exons of the PCNA gene was 76.8% in the region so far sequenced. The second one (psi-PCNA-II) consists of a region highly homologous to the entire exons of the PCNA gene, and only 9 out of total 1256 bp are different from the corresponding exon sequence of the gene. The 5'-flanking region of the psi-PCNA-II did not function as an active promoter. Surveys in various wild and laboratory mice genomes suggest that the psi-PCNA-II was generated through the reverse transcription process of the PCNA mRNA about 5 x 10(5) years ago in the domesticus subspecies of Mus musculus, the house mouse. The psi-PCNA-II is tentatively mapped in the chromosome 17 of the C57BL mouse.