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Nucleic Acids Research, 1992, Vol. 20, No. 17 4417-4421
© 1992

GENOME STRUCTURE AND MAPPING

Structure of the human DNA repair gene HAP1 and its localisation to chromosome 14q 11.2–12

Craig N. Robson, Daniel Hochhauser, Randa Craig, Katrina Rack1, Veronica J. Bukie1 and Ian D. Hickson*

Imperial Cancer Research Fund, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital Oxford OX3 9DU, UK 1MRC Molecular Haematology Unit, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital Oxford OX3 9DU, UK

*To whom correspondence should be addressed

Received June 26, 1992. Revised August 6, 1992. Accepted August 6, 1992.

Apurinic/apyrimidinic (AP) sites are pre-mutagenic DNA lesions which occur spontaneously and following exposure of cells to ionising radiation or chemical mutagens. HAP1 (Human AP endonuclease 1), the major enzyme in human cells initiating repair of AP sites, shows strong sequence homology to DNA repair enzymes from bacteria, Drosophila and other mammalian species. We have cloned the HAP1 gene and determined its complete nucieotide sequence. The site of transcription initiation has been mapped to 452 bp upstream of the ATG initiation codon in the genomic DNA. The HAP1 gene consists of five exons and is unusually small (less than 2.6 kb from transcription initiation site to polyadenylation sequence) with 54% of the protein coding region and the entire 3' untranslated region contained within a single exon. The first exon is non-coding. Regions of three exons show sequence homology to the E.coli xth (exonuclease III) gene. Using in situ hybridisation, the HAP1 gene has been localised to human chromosome 14q 11.2–12.


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