An expanding family of helicases within the 'DEAD/H' superfamily.

'DEAD/H' DNA and RNA helicases constitute a vast superfamily, with both prokaryotes, eukaryotes and viruses encoding numerous members involved in various aspects of genome replication, repair and expression (1, 2). Recently a variety of eukaryotic proteins with similarity to yeast protein Snf2 have been described (3-8), some of them involved in transcription regulation (Snf2, Sthl, YAL001, and Motl from yeast, human hSnf2I, and BRM from Drosophila), and in DNA recombination and repair (yeast Rad54, Radl6, Rad5, and Drosophila LDR). Specific variants of the seven sequence motifs typical of the 'DEAD/H' helicase superfamily (1) are conserved in these proteins. Using the sequence pattern of the variant of the ATP-binding motif A (helicase motif I) characteristic of this new family (uuxD[DE]uGuGKT; u a bulky aliphatic residue, i.e. 1, L, V, M) to screen the non-redundant amino acid sequence data base (National Center for Biotechnology Information), we found it in only one additional sequence, the putative E. coli helicase HepA (9). Alignment using the MACAW program (10) revealed four helicase motifs in the HepA sequence closely resembling the respective segments in the proteins of the new family (Figure). An additional motif shared by all these putative helicases was identified (lb in the Figure). Motifs IV to VI were absent in the published HepA sequence (9). Analysis of the sequence of the product of a long open reading frame (ORF) located downstream from the HepA ORF (11) using TFASTA (12) and TBLASTN (13) programs revealed significant similarity to the helicases of the new family, with obvious counterparts to motifs V and VI (Figure). Thus, we predict that these two ORFs actually comprise a single gene encoding a helicase belonging to the new family. Similarly, a probable frameshift was detected in the LDR gene sequence (14) allowing identification of motifs V and VI in the encoded helicase (Figure).