Topoisomerase IV
Encyclopedia
Topoisomerase IV is one of two type-II topoisomerase
s in bacteria, the other being DNA gyrase
. Like gyrase, topoisomerase IV is able to pass one double-strand of DNA through another double-strand of DNA, thereby changing the linking number
of DNA by two in each enzymatic step.
drugs, which include ciprofloxacin
.
Topoisomerase
Topoisomerases are enzymes that regulate the overwinding or underwinding of DNA. The winding problem of DNA arises due to the intertwined nature of its double helical structure. For example, during DNA replication, DNA becomes overwound ahead of a replication fork...
s in bacteria, the other being DNA gyrase
DNA gyrase
DNA gyrase, often referred to simply as gyrase, is an enzyme that relieves strain while double-stranded DNA is being unwound by helicase. This causes negative supercoiling of the DNA...
. Like gyrase, topoisomerase IV is able to pass one double-strand of DNA through another double-strand of DNA, thereby changing the linking number
Linking number
In mathematics, the linking number is a numerical invariant that describes the linking of two closed curves in three-dimensional space. Intuitively, the linking number represents the number of times that each curve winds around the other...
of DNA by two in each enzymatic step.
Functions
Topoisomerase IV has two functions in the cell.- First, it is responsible for unlinking, or decatenating, DNA following DNA replicationDNA replicationDNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
. The double-helical nature of DNADNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
and its semiconservative mode of replication causes the two newly replicated DNA strands to be interlinked. These links must be removed in order for the chromosomeChromosomeA chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
(and plasmids) to segregate into daughter cells so that cell division can complete.
- Topoisomerase IV's second function in the cell is to relax positive supercoils. It shares this role with DNA gyrase, which is also able to relax positive supercoils. Together, gyrase and topoisomerase IV remove the positive supercoils that accumulate ahead of a translocating DNA polymeraseDNA polymeraseA DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....
, allowing DNA replicationDNA replicationDNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
to continue unhindered by topological strain.
- DNA gyraseDNA gyraseDNA gyrase, often referred to simply as gyrase, is an enzyme that relieves strain while double-stranded DNA is being unwound by helicase. This causes negative supercoiling of the DNA...
s are analogous enzymes in other organisms.
Clinical significance
Topoisomerase IV is also a target of antibiotics, such as the quinoloneQuinolone
The quinolones are a family of synthetic broad-spectrum antibiotics. The term quinolone refers to potent synthetic chemotherapeutic antibacterials....
drugs, which include ciprofloxacin
Ciprofloxacin
Ciprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class.It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of...
.