Left-handed Z-DNA: structure and function

Z-DNA is a high energy conformer of B-DNA that forms in vivo during transcr iption as a result of torsional strain generated by a moving polymerase. An understanding of the biological role of Z-DNA has advanced with the discov ery that the RNA editing enzyme double-stranded RNA adenosine deaminase typ e I (ADAR1) has motifs specific for the Z-DNA conformation. Editing by ADAR 1 requires a double-stranded RNA substrate. In the cases known, the substra te is formed by folding an intron back onto the exon that is targeted for m odification. The use of introns to direct processing of exons requires that editing occurs before splicing. Recognition of Z-DNA by ADAR1 may allow ed iting of nascent transcripts to be initiated immediately after transcriptio n, ensuring that editing and splicing are performed in the correct sequence . Structural characterization of the Z-DNA binding domain indicates that it belongs to the winged helix-turn-helix class of proteins and is similar to the globular domain of histone-H5.