tumor cell biology program - Sylvester Comprehensive Cancer Center

Ezelle, HJ, Balachandran, S, Sicheri,
F, Polyak, SJ and Barber, GN. Analyzing
the mechanisms of interferoninduced
apoptosis using CrmA and hepatitis
C virus NS5A. Virology 281:124,
2001.
Balachandran, S, Porosnicu, M and
Barber, GN. Oncolytic activity of vesicular
stomatitis virus is effective against
tumors exhibiting aberrant p53, Ras, or
Myc function and involves the induction
of apoptosis. Journal of Virology
75:3474, 2001.
Barber, GN. Host defense, viruses
and apoptosis. Cell Death and Differentiation
8:113, 2001.
Lin, RT, Genin, P, Mamane, Y,
Sgarbanti, M, Battistini, A, Harrington,
WJ, Barber, GN and Hiscott, J. HHV-
8 encoded vIRF-1 represses the interferon
antiviral response by blocking
IRF-3 recruitment of the CBP/p300
coactivators. Oncogene 20:800, 2001.
Saunders, LR, Jurecic, V, and Barber,
GN. The 90-and 110-kDa human
NFAR proteins are translated from two
differentially spliced mRNAs encoded on
chromosome 19p13. Genomics 71:256,
2001.
Paul E. Boehmer, Ph.D.
Associate Professor of Biochemistry
and Molecular Biology
DESCRIPTION OF RESEARCH
Enzymology of DNA Replication
and Recombination: Helicases and
Accessory Proteins
Dr. Boehmer’s laboratory is using herpes
simplex virus type-1 (HSV-1) as a
model system to study the enzymology
of DNA replication and recombination
with particular emphasis on helicases and
their accessory proteins. Helicases catalyze
DNA unwinding thereby converting
inert duplex DNA into template
information for DNA replication or creating
single-stranded DNA for strandtransfer
reactions in homologous recombination.
HSV-1 is a large double-stranded
DNA virus that is extremely widespread
in the human population. HSV-1 causes
a variety of primary and recurrent infections
ranging from rather benign cold
sores to corneal blindness and encephalitis.
HSV-1 infections are particularly
severe in immuno-compromised individuals
such as AIDS patients.
HSV-1 encodes its own DNA polymerase,
a multi-faceted single-strand
DNA-binding protein (SSB), and two
DNA helicases. The first helicase possesses
sequence-specific DNA-binding
activity that targets it to the origins of
replication to initiate replication. The
second helicase is a multi-subunit enzyme
that is responsible for concomitant
unwinding and priming at the DNA replication
fork. His team is interested in
studying the molecular mechanisms by
which these helicases unwind DNA and
how they interact with other DNA replication
factors notably SSB and DNA
polymerase. In addition, they are interested
in solving the crystal structures of
these proteins.
They are also using HSV-1 to study
the enzymology of homologous recombination.
In HSV-1 it is predicted that
homologous recombination proceeds by
a single-strand annealing mechanism.
Consequently, we are interested in studying
the role of the HSV-1 DNA helicases
and SSB in promoting stand annealing
and branch migration reactions.
Finally, Dr. Boehmer’s team is using
the HSV-1 DNA replication enzymes to
study the mechanism of translesion replication.
Using lesions produced by the
anticancer drug cisplatin, they hope to
demonstrate that interactions between
replication fork enzymes can lead to
mutagenic bypass of cisplatin lesions and
thus account for the mutagenic properties
of this drug.
These studies will increase our understanding
of how DNA helicases perform
essential tasks during DNA
replication and recombination and may
also contribute to the development of
novel anti-viral compounds targeted
against herpes virus infections.
PUBLICATIONS
Bastide, L, Boehmer, PE, Villani, G
and Lebleu, B. Inhibition of a DNAhelicase
by peptide nucleic acids. Nucleic
Acids Research 27:551, 1999.
Lehman, IR and Boehmer, PE. Replication
of Herpes Simplex Virus DNA.
Journal Biological Chemistry 274:
28059, 1999.
White, EJ and Boehmer, PE.
Photoaffinity labeling of the herpes simplex
virus type-1 single-strand DNAbinding
protein (ICP8) with oligodeoxyribonucleotides.
Biochemical Biophysical
Research Communications
264:493, 1999.
Gourves, A-S, Tanguy, Le Gac, N,
Villani, G, Boehmer, PE and Johnson,
NP. Equilibrium binding of single
stranded DNA with HSV-1 coded single
stranded DNA binding protein. ICP8.
Journal Biological Chemistry 275:
10864, 2000.
Sampson, DA, Arana, ME and
Boehmer, PE. Cysteine 111 affects coupling
of single-stranded DNA binding
to ATP hydrolysis in the Herpes simplex
virus type-1 origin-binding protein. Journal
of Biological Chemistry 275:2931,
2000.
Arana, ME, Haq, B, Le, Gac, NT
and Boehmer, PE. Modulation of the
herpes simplex virus type-1 UL9 DNA
helicase by its cognate single-strand
DNA-binding protein, ICP8. Journal of
Biological Chemistry 276:6840, 2001.
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UM/Sylvester Comprehensive Cancer Center Scientific Report 2002