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Virol Res J 2017 Volume 1 Issue 3
International Virology Conference
October 30-31, 2017 | Toronto, Canada
Roles of cellular DNA replication proteins in papillomavirus DNA replication
Thomas Melendy
University at Buffalo, USA
O
ther than E1, the papillomavirus (PV) DNA helicase, and
E2, the PV transcriptional regulator (that also assists E1 in
recognizing the HPV origin of replication and assembling into
E1’s hexameric helicase configuration), PVs rely entirely on host
proteins to replicate their viral DNA. Much of what we know
about theenzymes involved in the synthetic stages of eukaryotic
DNA replication were initiated in studies using a similar small
DNA tumour virus, the polyomavirus, SV40. Studies on SV40
helped identifyand/or confirma role inDNAreplication for: DNA
polymerase alpha-primase (PolPrim), Topoisomerase I (TopoI),
the major cellular ssDNA binding complex (RPA), Replication
Factor C, Proliferating Cell Nuclear Antigen, DNA polymerase
delta (PolD), and others. Another cellular replication complexes
such as DNA polymerase epsilon (PolE), and origin recognition
and licensing factors such as: The Origin Recognition Complex,
The Mini-Chromosome, Maintenance proteins, Cdc45p, and
others, were not required. SV40 hijacks the cellular machinery
by its helicase binding to just RPA, TopoI and PolPrim, and the
remaining factors are recruited by secondary interactions.
A major focus of my laboratory has been on elucidating how
the PV DNA replication proteins, E1 and E2, interact with and
recruit the cellular replication proteins. We found that as with
SV40, the PV helicase, E1 binds to: RPA, TopoI and PolPrim; and
we have elucidated some of the mechanisms behind why these
interactions are so vital for viral DNA replication. Moreover, we
have recently discovered additional interactions unlike those
seen in the SV40 system, including interactions between E1
and PolD and PolE and the PV E2 transcription protein with
TopoI and PolE. These are highly novel as no other virus has
ever been shown to evolve to utilize PolE to replicate their
viral genomes, and E1 in particular confers a novel and highly
unusual stimulation to synthesis by the cellular PolE enzyme.
These findings show that PV DNA replication is actually quite
different than polyomavirus DNA replication, from a functional
and viral recruitment perspective; and show that PV DNA
replication is apparentlymore similar to cellular DNA replication
than polyomavirus (SV40) DNA replication. Further, our results
provide novel biochemical targets for development of new anti-
PV therapeutics.
Speaker Biography
Thomas Melendy has completed his PhD at UCLA, was a Post-doctoral Fellow with
Bruce Stillman (NAS and FRS) at Cold Spring Harbor Laboratory where he wrote and
published the seminal Nature article on DNA polymerase switching. He is currently
an Associate Professor at the University at Buffalo, where he continues his ground-
breaking work on the mechanisms of viral DNA replication. He is an AAAS Fellow,
Presidential Scholar, Damon Runyon Fellow, Roche Award winner, served on ACS
and NIH Review Panels, has held numerous NIH/ACS grants and career development
awards, and has published over 40 papers in highly reputed journals.
e:
tmelendy@buffalo.edu