TOPOISOMERASE PPTX

2.  Topoisomerases are enzymes that release the tension in DNA strands. Where as
Helicases seperates the DNA strands. When a DNA strand undergoes replication or
transcription, the strand that is ahead of the replication fork starts to owerwind. If the
overwinding is not detangled, the torsion in the DNA strands will destroy the strand and
render it non-functional.
 Topoisomerases maintain the overall topology of DNA strands. The enzymes work by
binding to the DNA strands and breaking the phosphate bond of either one or both
strands. This allows the DNA to untangle and then the ends are again resealed. They do
not require any energy for this process.

3. Helicase Topoisomerase
 Helicases are enzymes that separate the nucleic acid
strands for replication.
 Topoisomerases are enzymes that relax the supercoiling
in DNA strands
 It utilises energy from the hydrolysis of nucleoside
triphosphates to translocate through the DNA
strands.
 Topoisomerase I does not utilise energy, but
Topoisomerase II does as it cuts both strands in DNA.
 It is divided into 6 superfamilies.  Type I and type II
 It breaks the hydrogen bonds between the
nucleotide bases.
 It breaks the phosphate backbone of either one or both
strands to detangle the DNA strands.
 It separates both double-stranded DNA and self
annealed RNA strands.
 It unwinds DNA only.
 It separates the DNA or RNA strands
for replication and recombination.
 It maintains the overall topology of the DNA strands.
 DNA helicase and RNA helicase.  Topoisomerase I and Topoisomerase II.

4. Topoisomerases are nuclear enzymes that play essential roles in DNA replication,
transcription, chromosome segregation, and recombination.
Forms of topoisomerases:
 Type I, which makes single-stranded cuts in DNA, and
 Type II enzymes, which cut and pass double-stranded DNA.

5.  These topoisomerases are capable of relaxing supercoiled DNA and of decatenating
interlocked DNA.
 Topoisomerases are important targets for many chemotherapeutic agents and
antibiotics.
 Both type I and type II topoisomerases can relax supercoiled DNA.
 Fluoroquinolones are potent inhibitors of prokaryotic type II topoisomerases, and are
commonly employed broad-spectrum antibiotics.

6.  Type I topoisomerases are enzymes that cut one of the two strands of double-stranded
DNA, relax the strand, and reanneal the strand.
 Type II topoisomerases are topoisomerases that cut both strands of the DNA helix
simultaneously in order to manage DNA tangles and supercoils. They use the
hydrolysis of ATP, unlike Type I topoisomerase. In this process, these enzymes change
the linking number of circular DNA by ±2. Topoisomerases are ubiquitous enzymes,
found in all living organisms.

9. Functions of Topoisomerase I :
 To remove DNA supercoils during transcription and DNA replication;
 For strand breakage during recombination;
 For chromosome condensation; and
 To disentangle intertwined DNA during mitosis.

15. Inhibition of Topoisomerase Enzyme:
Some chemical compounds can inhibit the functional roles of topoisomerases in organisms.
They commonly do it by hindering the DNA ligation step. Some examples of such chemicals
are:
• Protein inhibitors interfere with the DNA binding ability of the enzyme or stabilize the
cleavage complex. Its examples are bacterial toxins MccB17, ParE, and YacG.
• Doxorubicin and its derivatives inhibit the functions of the human topoisomerases by
stabilizing the cleavage complex.
• The quinolone class of antibiotics inhibits topoisomerase activity by preventing the
religation of broken DNA strands, which can cause mutation.
• Mitoxantrone diacetate, which inhibits protein kinase activity, is also a type of potent
topoisomerase II inhibitor.

17. Functions of Topoisomerases
Type I Topoisomerase Functions:
•They are involved in the removal of supercoils of DNA in biological processes such as
replication and transcription.
•Help in relaxing DNA.
•They help in breaking strands during recombination.
•They are also involved in the condensation of the chromosome.
•During mitosis, the DNA strands need to be free from interwinding which is done by
topoisomerase I.

18. Type II Topoisomerase Functions:
•It increases the disentanglement of the chromosome.
•It does not aid in the supercoiling of DNA but is involved in their relaxation.
•DNA gyrase promotes the negative supercoils of DNA.
•One of the most important functions is that it brings the change of two units in the linking
number of loops in DNA.

19. Thank You