ERCC1: A comparative genomic perspective

ERCC1 plays an essential role in the nucleotide excision repair (NER) of DN A. We compare 37 kb of sequence from the ERCC1 region on human chromosome 1 9q13.3 to the orthologous region on mouse chromosome 7. In addition to show ing the conserved gene structure between ERCC1, ASE-1, and their murine cou nterparts, this genomic comparison reveals a highly conserved 497 by segmen t found 5 kb upstream of ERCC1 exon 1 that contains a CpG island and previo usly unidentified "classical" promoter elements. Additional putative regula tory elements are also found within a conserved LINE-1 (long interspersed n uclear element) sequence 800 by upstream of exon 1 in both human and mouse. Expressed sequence tag (EST) assemblies for human ERCC1 identified numerou s splice variants involving exons 1, 2, 3, 7, 8, and 9 that could affect DN A repair efficiencies of ERCC1. A previously undescribed transcript that re ads through exon 9 and utilizes the polyadenylation signal of a neighboring Alu element accounts for nearly half of the total splice variants identifi ed in the human EST database. This transcript would theoretically translate to a larger ERCC1 protein product containing a novel C-terminal end. Overa ll, approximately 18% of publicly available ERCC1 cDNA sequences were deter mined to be splice variants, while no variants were found in the mouse. The ability to assess novel transcripts and identify candidate regulatory regi ons demonstrates the potential utility for a catalogue archiving comparativ e analyses for all genes involved in DNA repair. Our comparative genomic an alysis of ERCC1 can be viewed at http://web.uvic.ca/ similar to bioweb/laj. html. 2001 Wiley-Liss, Inc.