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Hepatitis B Virus (HBV) X protein (pX) is implicated by an unknown mechanism in hepatocellular carcinoma (HCC) development, characterized by increased rate of chromosomal aberrations. Although most patients clear the infection and develop immunity, chronic infection in 5 to 10% infected patients lead to HCC development in the 4th to 5th decade of life. I demonstrate that tetracycline-regulated pX expression induces multipolar spindles and polyploidy ( 4N DNA). To understand the mechanism of pX-mediated polyploidy, I investigated whether pX promotes DNA re-replication. Dual-parameter flow…mehr

Produktbeschreibung
Hepatitis B Virus (HBV) X protein (pX) is implicated
by an unknown mechanism in
hepatocellular carcinoma (HCC) development,
characterized by increased rate of
chromosomal aberrations. Although most patients clear
the infection and develop
immunity, chronic infection in 5 to 10% infected
patients lead to HCC development in
the 4th to 5th decade of life. I demonstrate that
tetracycline-regulated pX expression
induces multipolar spindles and polyploidy ( 4N DNA).
To understand the mechanism
of pX-mediated polyploidy, I investigated whether pX
promotes DNA re-replication.
Dual-parameter flow cytometry demonstrates
pX-dependent BrdU incorporation in cells
with 4N DNA. pX also induces expression of
replication initiation factors Cdc6 and
Cdtl, while suppressing geminin expression, a
negative regulator of re-replication. G2-
phase synchronized cells exhibit pX-dependent: i)
nuclear Cdc6 and Mcm5 colocalization;
ii) absence of nuclear geminin; iii) increased BrdU
incorporation; iv) ATR
activation; v) RAD17 and H2AX phosphorylation; and
vi) co-localization of -H2AX
with the DNA elongation factor PCNA.
Autorenporträt
Lova Rakotomalala was born in Nice in 1977. Lova obtained a
Bachelor in Science from Tulane University and his PhD from
Purdue University. Lova is currently a post-doctoral fellow at
Purdue University. He is working on two projects:1)
the development of low-cost CD4 counter 2)cervical cancer
detection combining flow cytometry and PCR genotyping.