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Journal of Medical Oncology and Therapeutics | Volume: 3
July 23-25, 2018 | Moscow, Russia
12th World Cancer Congress
Role of DNA/RNA- lipids interactions in Nuclear pore assembly, Genome expression and Cancer cell
degeneration
Vasily Kuvichkin
Russian Academy of Sciences, Russia
During the study of the ternary complexes-TC: nucleic
acids - liposomes from zwitterionic lipids, in the presence
of a number of divalent metal cations- (Ca, Mg, Fe, Co, etc),
the author concluded about the uniqueness and widespread
prevalence of such complexes in the cell. They are more
labile than lipoplexes-complexes of cationic lipids with DNA,
in addition have a more diverse structure and are more
dynamic, capable of creating various organelle-like structures,
or contacts between organelles in eukaryotes. In addition, TCs
are not toxic to cells, unlike lipoplexes. The author suggested a
possible scheme for the formation of nuclear pores involving
liposomes from zwitterionic lipids and double-stranded DNA
or triple-stranded hybrids DNA /low molecular weight RNA
(lmw RNA), which, when untwisted in pore annuli, give one or
two chains of ssDNA. The thermo-stability of DNA/lmwRNA
triple helix is lower than the same sequence of DNA. That
specifies preferential attachment of three-stranded hybrids
to membrane vesicles. The triple helical hybrid unwinding
during fusion of two membrane vesicles results in pre-pore
formation: double-stranded DNA/lmwRNA hybrid and a ssDNA
(R-loop), located on the outer diameter of fused vesicle of TC.
This vesicle interacting with double nuclear membrane form
channel between two membranes. During their fusion ssDNA
and hybrid of DNA/lmwRNA shifts to pore annulus center and
serve as template for nucleoporins binding and for gradually
pore complex formation. The ssDNA in pore annulus is the
reason for the enhanced transcription of the genes attached
to nuclear pore. The ssDNA located along the outer diameter
of TC vesicles serve as sites of transcription initiation and their
aggregates can be considered as “transcription factories”.
Increasing of number nuclear pore during cancer progression
means increasing of transcription of specific oncogenes in a
cell. Pore can form cluster from 10-12 pores, which manifold
increase a transcription of near to cluster genes. The presence
in nuclear pores lmwRNA (small nuclear RNA or long non-
coding RNA) give us possibility of their participation in
changing activity of genes in cancer cells. Change of lmwRNA
between cancer and normal cells allow these RNA induced
cancer in normal cells by mechanisms of chains reaction.
Many membrane tropic carcinogens increase transcriptional
activity pore complex as their production and stability in cells.
Speaker Biography
Vasily Kuvichkin has completed his PhD at the age of 35 years at Moscow State
University, Lomonosov’s name, Russia. He is the chief of Group of lipids-nucleic
acids interactions at the Institute of Cell Biophysics, Russian Acadey of Sciences.
He has over 120 publications that have been cited over 600 times. He is member
of Biophysical Society, Japanese Society Molecular and Cell Biology and FEBS.
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