Cloning and characterization of HARP/SMARCAL1: A prokaryotic HepA-related SNF2 helicase protein from human and mouse

The SNF2 gene family consists of a large group of proteins involved in tran scriptional regulation, maintenance of chromosome integrity, and various as pects of DNA repair. We cloned a novel SNF2 family human cDNA, with sequenc e identity to the Escherichia coli RNA polymerase-binding protein HepA and named the human hepA-related protein (HHARP/SMARCAL1). In addition, the mou se ortholog (Mharp/Smarcal1) was cloned, and the Caenorhabditis elegans ort holog (CE-HARP) was identified in the GenBank database. Phylogenetic analys is indicates that the HARP proteins share a high level of sequence similari ty to the seven motif helicase core region (SNF2 domain) with identifiable orthologs in other eukaryotic species, except for yeast. Purified His-tagge d HARP/SMARCAL1 protein exhibits single-stranded DNA-dependent ATPase activ ity, consistent with it being a member of the SNF2 family of proteins. Both the human and the mouse genes consist of 17 exons and 16 introns, The huma n gene maps to chromosome 2q34-q36, and the mouse gene is localized to the syntenic region of chromosome 1 (between markers Gls and Acrg). HARP/SMARCA L1 transcripts are ubiquitously expressed in human and mouse tissues, with testis presenting the highest levels of mRNA expression in humans. (C) 2000 Academic Press.