Structure function analysis of the HSV-1 UL52 zinc finger domain
Date of Completion
January 2004
Keywords
Biology, Molecular|Biology, Microbiology|Chemistry, Biochemistry
Degree
Ph.D.
Abstract
The HSV-1 helicase-primase is a trimeric complex consisting of the products from UL5, UL8 and UL52 genes. These genes are essential for HSV-1 DNA replication and perform many functions during the viral DNA replication process. UL5 is believed to be the helicase based on the presence of seven conserved helicase motifs, UL8 has no known enzymatic activities, while UL52 is believed to be the primase subunit of the complex. UL52 contains a conserved primase catalytic domain found in both primases and polymerases. It also contains a zinc finger domain similar to those observed in prokaryotic and eukaryotic primases. This primase domain is highly conserved among members of the herpesviridae, and in our genetic and biochemical analyses of the zinc finger motif we determined it to be required not only for the primase activity of the helicase-primase complex, but also the helicase, ATPase and DNA binding activities of the complex. The data obtained in our study also show that polymerase recruitment to the replication fork is dependent on the UL52 subunit as mutations in either the catalytic site or the zinc binding domain result in the inefficient recruitment of the HSV-1 polymerase, UL30, to replication intermediates. We hypothesize based on the results of this study that the UL52 zinc finger domain is likely a DNA binding domain that is essential for the functions of the entire helicase-primase complex. ^
Recommended Citation
Carrington-Lawrence, Stacy Dawn, "Structure function analysis of the HSV-1 UL52 zinc finger domain" (2004). Doctoral Dissertations. AAI3156379.
https://digitalcommons.lib.uconn.edu/dissertations/AAI3156379