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Journal of Clinical and Experimental Toxicology | Volume: 2
December 03-04, 2018 | Dubai, UAE
International Conference on
6
th
International Conference on
Toxicology, Clinical Toxicology & Pharmacology
Recycling & Waste Management
Joint Event
&
The target of many toxins and drugs is R-loop opening area in nuclear pores
Kuvichkin V
Russia Academy of Sciences, Russia
T
he ternary complexes (TC): DNA- phosphatidylcholine (PC)
liposomes- divalent metal cations unlike lipoplexes are only
lately has received attention. We proposed their involvement in
the nuclear pore assembly. The formation of TC accompanied
by the aggregation and fusion of PC liposomes was shown by
freeze-etching and cryo- TEM technique. At the same time,
double helix of DNA unwinds in the region of liposomes fusion
that enhances initiation of DNA transcription. Membrane
vesicles forming the nuclear pores in a cell are analog of PC
liposomes. In our last nuclear pore model TC arises in the
chromatin areas with three-stranded hybrids: DNA – small
nuclear RNA (snRNA) at their interactions with two small
membrane vesicles (~70 nm in diameter). The thermo stability
of DNA/snRNA triple helix is considerably lower than the same
sequence of double- stranded 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-
strandedDNA/snRNAhybridandasingle- strandedDNA(ssDNA)
located on the outer diameter of fused “big vesicle”. This vesicle
during interaction with double nuclear membrane can form
channel between membranes. During this fusion ssDNA and
hybrid, DNA/snRNA shifts to pore annulus center. The ssDNA
in pore annulus is the reason for the enhanced transcriptional
activity of the genes neighboring nuclear pore. The number
of pores in a nucleus specifies chromosome territory and
number of chromosome loops. Nuclear pores serve as sites of
the initiation of transcriptions in a cell, because ssDNA is the
best site of transcription initiation than dsDNA with the same
nucleotide sequence. Binding of many toxic substances to
ssDNA can prevent transcription initiation in area of nuclear
pores. Using TCs as nuclear pore precursors we can made easy
and sensitive test system for finding toxins and anti-toxicants.
e:
vvkuvichkin@gmail.comToxicology 2018 & Recycling 2018, Volume 2
DOI: 10.4066/2630-4570-C1-003