Open AccessA 128-Base-Pair Sequence Containing the pac1 and a Presumed Cryptic pac2 Sequence Includes cis Elements Sufficient To Mediate Efficient Genome Maturation of Human Cytomegalovirus
Author(s) -
Jian Ben Wang,
Michael A. McVoy
Publication year - 2011
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.02307-10
Subject(s) - biology , cleavage (geology) , genome , human cytomegalovirus , concatemer , dna , genetics , dna replication , capsid , cleavage factor , cleavage and polyadenylation specificity factor , conserved sequence , microbiology and biotechnology , polyadenylation , gene , rna , base sequence , paleontology , fracture (geology)
Herpesvirus DNA replication proceeds via concatemeric replicative intermediates that are comprised of head-to-tail linked genomes. Genome maturation is carried out by the terminase, an enzyme complex that mediates both the insertion of concatemer DNA into capsids and its subsequent cleavage to release genomes within these capsids. This cleavage is sequence specific, but the governingcis -acting DNA sequences are only partially characterized. Two highly conserved motifs, thepac1 andpac2 motifs, lie near the ends of herpesvirus genomes and are known to be critical for genome maturation. In murine cytomegalovirus, poorly conserved sequences distal to thepac2 motif up to 150 bp from the point of cleavage are also important for cleavage. Here, we sought to identify the cleavage/packaging signals of human cytomegalovirus. Our results show that a previously proposedpac2 -like poly(A) tract is dispensable for cleavage/packaging function and suggest that human cytomegalovirus may utilize a crypticpac2 motif that lacks a poly(A) tract characteristic ofpac2 motifs in other herpesviruses. Additional distal sequences 47 to 100 bp from the point of cleavage were found to enhance cleavage efficiency. These results should facilitate the identification oftrans -acting factors that bind to thesecis elements and elucidation of their functions. Such information will be critical for understanding the molecular basis of this complex process.