ERCC1: A comparative genomic perspective

ERCC1 plays an essential role in the nucleotide excision repair (NER) of DNA. We compare 37 kb of sequence from the ERCC1 region on human chromosome 19q13.3 to the orthologous region on mouse chromosome 7. In addition to showing the conserved gene structure between ERCC1, ASE-1, and their murine counterparts, this genomic comparison reveals a highly conserved 497 bp segment found 5 kb upstream of ERCC1 exon 1 that contains a CpG island and previously unidentified "classical" promoter elements. Additional putative regulatory elements are also found within a conserved LINE-1 (long interspersed nuclear element) sequence 800 bp upstream of exon 1 in both human and mouse. Expressed sequence tag (EST) assemblies for human ERCC1 identified numerous splice variants involving exons 1, 2, 3, 7, 8, and 9 that could affect DNA repair efficiencies of ERCC1. A previously undescribed transcript that reads through exon 9 and utilizes the polyadenylation signal of a neighboring Alu element accounts for nearly half of the total splice variants identified in the human EST database. This transcript would theoretically translate to a larger ERCC1 protein product containing a novel C-terminal end. Overall, approximately 18% of publicly available ERCC1 cDNA sequences were determined to be splice variants, while no variants were found in the mouse. The ability to assess novel transcripts and identify candidate regulatory regions demonstrates the potential utility for a catalogue archiving comparative analyses for all genes involved in DNA repair.