SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

V I R A L O N C O L O G Y P R O G R A M
SELECTED PUBLICATIONS
2002
Carastro, LM, Tan, CK, Selg, M, Jack, HM, So,
AG, and Downey, KM. Identification of delta
helicase as the bovine homolog of HUPF1: demonstration
of an interaction with the third subunit
of DNA polymerase delta. Nucleic Acids
Research 30:2232-43, 2002.
Meyer, PR, Matsuura, SE, Tolun, AA, Pfeifer, I,
So, AG, Mellors, JW, and Scott, WA. Effects of
specific zidovudine resistance mutations and substrate
structure on nucleotide-dependent primer
unblocking by human immunodeficiency virus
type 1 reverse transcriptase. Antimicrobial Agents
and Chemotherapy 46:1540-5, 2002.
Lu, X, Tan, CK, Zhou, JQ, You, M, Carastro,
LM, Downey, KM, and So, AG. Direct interaction
of proliferating cell nuclear antigen with the
small subunit of DNA polymerase delta. Journal
of Biological Chemistry 277:24340-5, 2002.
HIGHLIGHTS/DISCOVERIES
• Demonstrated a direct interaction between the
small subunit of human DNA polymerase delta
(p50) and PCNA, a marker for cell proliferation,
by reciprocal co-immunoprecipitation of
the two proteins using antibodies against either
p50 or PCNA, suggesting that this interaction
is primarily responsible for processive DNA
synthesis by DNA polymerase delta. Researchers
in Dr. So’s laboratory have now confirmed
that this interaction readily occurs in cells. This
is important because the interaction of DNA
polymerase delta with PCNA is at the core of
replication machinery (replisome) function and
crucial to our understanding of how DNA replication
is coordinated with DNA repair and
cell cycle progression.
• Identified a novel 36-kDa protein, designated
polymerase delta interacting protein 1 (PDIP1)
that physically and functionally interacts with
both PCNA and the 50-kDa subunit of DNA
polymerase delta, both in vitro and in vivo.
Researchers further have shown the expression
of this protein is induced by tumor necrosis factor
α (TNF-α) and interleukin-6 (IL-6). These
cytokines are essential for growth and proliferation
of many cell types and implicated in the
tumorigenesis of a number of cancers, including
AIDS-related non-Hodgkin’s lymphoma and
multiple myeloma. Thus, PDIP1 is a potential
target for the development of novel therapeutic
agents for the treatment of these tumors.
UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 141