HEX1 - A NEW HUMAN RAD2 NUCLEASE FAMILY MEMBER WITH HOMOLOGY TO YEASTEXONUCLEASE-1

Nucleolytic processing of chromosomal DMA is required in operations su ch as DNA repair, recombination and replication. We have identified a human gene, named HEX1 for human exonuclease 1, by searching the EST d atabase for cDNAs that encode a homolog to the Saccharomyces cerevisia e EXO1 gene product. Based can its homology to this and other DNA repa ir proteins of the Rad2 family most notably Schizosaccharomyces pombe exonuclease 1 (Exo1), Hex1 presumably functions as a nuclease in aspec ts of recombination or mismatch repair. Similar to the yeast proteins, recombinant Hex1 exhibits a 5'-->3' exonuclease activity. Northern bl ot analysis revealed that HEX1 expression is highest in fetal liver an d adult bone marrow, suggesting that the encoded protein may operate p rominently in processes specific to hemopoietic stem cell development. HEX1 gene equivalents were found in all vertebrates examined. The hum an gene includes 14 exons and 13 introns that span similar to 42 kb of genomic DNA and maps to the chromosomal position 1q42-43, a region lo st in some cases of acute leukemia and in several solid tumors.