Herpesviruses have large double-stranded linear DNA genomes that are formed by 
site-specific cleavage from complex concatemeric intermediates. In this process, 
only one of the two genomic ends are formed on the concatemer. Although the 
mechanism underlying this asymmetry is not known, one explanation is that single 
genomes are cleaved off of concatemer ends in a preferred direction. This 
implies that cis elements control the direction of packaging. Two highly 
conserved cis elements named pac1 and pac2 lie near opposite ends of herpesvirus 
genomes and are important for cleavage and packaging. By comparison of published 
reports and by analysis of two additional herpesviruses, we found that pac2 
elements lie near the ends formed on replicative concatemers of four 
herpesviruses: herpes simplex virus type 1, equine herpesvirus 1, guinea pig 
cytomegalovirus, and murine cytomegalovirus. Formation of pac2 ends on 
concatemers depended on terminal cis sequences, since ectopic cleavage sites 
engineered into the murine cytomegalovirus genome mediated formation of pac2 
ends on concatemers regardless of the orientation of their insertion. These 
findings are consistent with a model in which pac2 elements at concatemer ends 
impart a directionality to concatemer packaging by binding proteins that 
initiate insertion of concatemer ends into empty capsids.