The mammalian FEN-1 locus: structure and conserved sequence features.

Abstract

Flap endonuclease 1 (FEN-1) is an enzyme that is very important for DNA replication in all eukaryotes because it cleaves the 5' DNA flaps that arise between Okazaki fragments. In addition, FEN-1 is important for base excision repair and for nonhomologous DNA end joining in all eukaryotes from yeast to human. Here we report the structure and sequence of the murine genomic FEN-1 locus, and we compare it to the human FEN-1 locus. The transcriptional initiation zone of FEN-1 is within a CpG island, and the coding region of FEN-1 is a single exon in both the murine and human genomes. There are striking regions of nucleotide sequence homology within the 5' or 3'UTR or immediately upstream of the 5'UTR. These regions range from 30 to 230 bp. The functions of these conserved sequence blocks could be in transcriptional regulation, or they may represent a gene that overlaps in its initiation zone with FEN-1, but is oriented in the opposite transcriptional direction.