Biology Reference
In-Depth Information
Nuts and Bolts of Human Cytomegalovirus
Lytic DNA Replication
G. S. Pari
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
Essential Region I: IE2-UL84 Responsive Promoter in oriLyt . . . . . . . . . . . . . . . . . . . . . . . . 155
Essential Region II: RNA/DNA Hybrid Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
Viral-Encoded
trans
-Acting Factors Required for Lytic Replication . . . . . . . . . . . . . . . . . . . 159
UL84 and IE2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Viral and Cellular Encoded UL84 Binding Partners . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
Summary and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
Abstract
HCMV lytic DNA replication is complex and highly regulated. The
cis
-acting lytic origin of DNA replication (oriLyt) contains multiple repeat
motifs that comprise two main functional domains. The first is a bidirectional
promoter element that is responsive to UL84 and IE2. The second appears to be
an RNA/DNA hybrid region that is a substrate for UL84. UL84 is required for
oriLyt-dependent DNA replication along with the six core proteins, UL44 (DNA
processivity factor), UL54 (DNA polymerase), UL70 (primase), UL105 (helicase),
UL102 (primase-associated factor) and UL57 (single-stranded DNA-binding pro-
tein). UL84 is an early protein that shuttles from the nucleus to the cytoplasm, binds
RNA, suppresses the transcriptional activation function of IE2, has UTPase activity
and is proposed to be a member of the DExH/D box family of proteins. UL84 is a
key factor that may act in concert with the other core replication proteins to initiate
lytic replication by altering the conformation of an RNA stem loop structure within
oriLyt. In addition, new data suggests that UL84 interacts with at least one member
of the viral replication proteins and several cellular encoded proteins.
G. S. Pari
University of Nevada, Reno, School of Medicine, Reno NV 89557 , USA
gpari@med.unr.edu
