Cover photograph (Copyright © 2002, American Society for Microbiology. All Rights Reserved.): Structure of the hepatitis C virus RNA polymerase in complex with nucleotides. The protein backbone is colored according to domains. Bound nucleotides are shown as ball-and-stick structures. Divalent metals appear as large gray spheres. The experimental density is shown as a green net. The nucleotides match strikingly well the catalytic and priming sites observed in the initiation complex of the bacteriophage φ6 polymerase, strengthening the proposal that the two enzymes initiate replication de novo by similar mechanisms. Three residues (labeled) contacting the nucleotide at the priming site are strictly conserved in many polymerases of other positive-stranded RNA viruses and are proposed to constitute the signature of a large class of RNA polymerases capable of de novo initiation. Also shown (in light gray) is the location of a specific, remote GTP binding site. (See related article on p. 3482.)