Research Interests

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Research Interests Assist. Prof. Dr. Sevim Isik
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Education BS, Bogazici University, Molecular
Biology Genetics-1995, Istanbul/Turkey MS,
Istanbul University, Oncology Institute,
Oncological Biology Immunology, Istanbul/Turkey
PhD, Okayama University, Medical School,
Cellular and Molecular Biology Institute,
Molecular Biology Department-2003,
Okayama/JAPAN
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• Selected Publications
• Academics Journals
• Isik S, Sano K, Tsutsui K, Seki M, Enomoto T,
  Saitoh H, tsutsui K, "The SUMO pathway is
  required for selective degradation of DNA
  topoisomerase IIbeta induced by a catalytic
  inhibitor ICRF-193(1)", FEBS Lett. , Vol.
  546(2-3), Jul. 2003, pp. 374-8.
• Tohge H, Tsutsui K, Sano K, Isik S, Tsutsui K. ,
  "High incidence of antinuclear antibodies that
  recognize the matrix attachment region", Biochem
  Biophys Res Commun., Vol. 285, No. 1, Jul. 2001,
  pp. 64-9

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Courses Taught 2006-2007 "Special Topics in
Biology (Essentials of Stem Cell Biology)", BIOL
502, Credit3 2006-2007 "Introduction to
Cellular Molecular Biology", BIOL 203, Credit3
2006-2007 "Physiology I Lab.", BIOL 303,
Credit1 2006-2007 "Introduction to Cellular
Molecular Biology Lab.", BIOL 253, Credit2
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MS Thesis Berrak
Tanrisever, "Effect of shear stress on the
expression and localization of V-cadherins and
alpha5 / beta1integrin on endothelial cells",
Fatih University, Oct. 2007
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Research Projects The Role of Topo IIb in
Neural Transdifferentiation Related Gene
Transcription of Human Mesenchymal cells,
TUBITAK-, Ana Yönetici Effect of shear stress on
the expression and localization of integrin
alpha5/beta1and v-cadherins, Master thesis-, Oct
2006-Dec 2007. Denizel kirleticilerin genotoksik
etkilerini in vivo ve in vitro sartlarda DNA
hasarini izleyerek saptamak için model sistemler
ve rutine geçebilecek midye izleme yöntemleri
olusturma, TUBITAK-, Yardimci Yönetici
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The SUMO pathway is required for selective
degradation of DNA topoisomerase IIb induced by a
catalytic inhibitor ICRF-193
PhD. Thesis Sevim Isik Department of Molecular
Biology Okayama University, Medical School,
Cellular and Molecular Biology Institute
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Redistribution of topo IIb induced by ICRF-193
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Expression of topo IIb in granule cells
differentiating in vitro
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Functions of Topoisomerases

• DNA Replication
• Chromatin Condensation
• Segregation of Chromosomes during mitosis and
  meiosis
• Transcription
• Recombination
• DNA Repair

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Reactions catalyzed by DNA topoisomerase II
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Reactions catalysed by topoisomerases
Knotting irreducible entanglement of a single
DNA molecule
Type I or Type II topo
knotting
unknotting
Catenation the linking of two or more DNA
molecules in which at least one strand of each
dublex is in the form of a closed ring
Type II topo
catenation
decatenation
If one strand is nicked, only then topo I
catalyse catanation or decatanation
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Transcription
Free rotation can not occur in vivo
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Elongation of replication
Precatenanes and () supercoils are formed in
front of replication fork.
leading strand
lagging strand
positive supercoils

precatenanes

negative supercoils
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Topo II-specific inhibitors used in the study
Cleavable complex
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Topo IIb is degraded via proteasome in granule
cells treated with ICRF-193
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Selective degradation of topo IIb in HeLa cells
treated with ICRF-193
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The ICRF-induced topo IIb degradation in HeLa
cells proceeds rapidly
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Slower time course of topo IIb degradation in
granule cells
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ICRF-193 induces multiple modifications on topo
IIb
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The ICRF-induced topo IIb degradation is
abrogated in Ubc9-deficient cells
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DNA topoisomerase II? It is a very important
enzyme for the promotion of gene transcription
during cell differentiation.
Topo II ?
turn on
Gene transcription During cell differentiation
Topo II ? inactivation
Turn off Cell differentiaiton is inhibited
Gene transcription During cell differentiation
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Research Interests Cell differentiation (stem
cells) Cell motility (cell adhesion molecules
such as integrins) Extracellular matrix Stem
cells Embryonic stem cells Adult stem cells
bone marrow, peripheral blood, brain, spinal
cord, dental pulp, blood vessels, skeletal
muscle, epithelia of the skin and digestive
system, cornea, retina, liver, and pancreas
Umblical cord stem cells Fetal stem cells
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Tissue engineering Therapeutic purposes
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Mesenchymal stem cells bone marrow
Can also differentiate into other cell types such
as neurons
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Mesenchymal stem cells can differentiate into
nerve cells
Neuron
Mesenchymal stem cells
Transdifferentiation
Topo II ? inactivation
Stop differentiaiton at different stages of
differentiation
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Some of the techniques which will be used in the
project Inhibition of Topo II? expression by
siRNAs (transfection)- very new method, topo IIb
specific Expression of topo II? in mesenchymal
and neural cells SDS-PAGE and western
blot Immunostaining staining of cell specific
of molecular markers with flourecent antibodies
during differentiation RNA isolation, Real time
PCR- quantitative analysis the expression of
genes during differentiation Microarray analysis
expression of the genes during differentiation