Genomic structure of the rat major AP endonuclease gene (Apex) with an adjacent putative O-sialoglycoprotease gene (Prsmg1/Gcpl1) and a processed Apex pseudogene (Apexp1)

Genomic sequencing and chromosomal assignment of the gene encoding rat APEX nuclease, a multifunctional DNA repair enzyme, were performed. An active A pex gene and a processed pseudogene were isolated from a rat genomic librar y. The active Apex gene consists of 5 exons and 4 introns spanning 2.1 kb. The putative promoter region of the Apex gene lacks the typical TATA box, b ut contains CAAT boxes and a CpG island having putative binding sites for s everal transcription factors, such as Spl, AP-2, GATA-1 and ATF. A putative O-sialoglycoprotease (a homologue of Pasteurella haemolytica glycoprotease , gcp; abbreviated as Prsmg1 / Gcpl1)gene consisting of 11 exons and 10 int rons spanning 7.3 kb lies immediately adjacent to the Apex gene in a 5'-to- 5' orientation. The Apex gene locus was mapped to rat chromosome 15p12 usin g in situ hybridization. The processed pseudogene (designated as rat Apexp 1)has a nucleotide sequence 87.1% identical to that of the rat Apex cDNA, a lthough several stop codons interrupting the coding sequences and multiple nucleotide deletions were observed. The Apexp1 is located in an inactive LI NE sequence. Calculation of nucleotide substitution rates suggests that the immediate, active progenitor of Apexp 1 arose 23 million years ago and tha t the non-functionalization occurred 15 million years ago.