What is the function of topoisomerase I?
Topoisomerase 1 (TOP1) is a highly conserved enzyme that can be found in both prokaryotes and eukaryotes. In the mammalian system, TOP1 is an essential enzyme for normal development [1]. A major function of TOP1 is to relax supercoiled DNA and alleviate the DNA helical constraints [2], [3].
What does topoisomerase do in bacteria?
Topoisomerases are ubiquitous enzymes that are responsible for maintaining the optimal supercoiling level of DNA inside the cell. They are important in cellular processes such as DNA replication, transcription, and repair, and maintenance of genome integrity.
Do bacteria have topoisomerase 1?
Topo I is present in all bacteria and is the major activity responsible for removal of excess negative supercoiling (13). In Escherichia coli, the promoters of topo I and gyrase genes are under homeostatic control by DNA supercoiling to maintain the global level of supercoiling (14,15).
What is the role for bacterial topoisomerase I in DNA replication?
Topoisomerases are needed in all three phases of bacterial DNA replication: initiation at the origin of replication, elongation with progressive outward movement of the forks until they meet halfway around the chromosome, and termination, including the final disentanglement of the catenated daughter chromosomes.
What is the function of topoisomerase I and II?
Topoisomerase IIα is found at replication forks and remains tightly associated with chromosomes during mitosis [13,39]. Thus, topoisomerase IIα is believed to be the isoform that functions in growth-dependent processes, such as DNA replication and chromosome segregation [7,13].
What is the difference between topoisomerase 1 and 2?
Definition. Topoisomerase I refers to the enzymes which cut one of the two strands of double-stranded DNA, relax the strand, and reanneal the strand while topoisomerase II refers to the enzymes which cut both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils.
What is the function of topoisomerase 1 and 2?
What do topoisomerase inhibitors do?
Topoisomerase inhibitors (TI) can inhibit cell proliferation by preventing DNA replication, stimulating DNA damage and inducing cell cycle arrest. Although these agents have been commonly used in the chemotherapy for the anti-proliferative effect, their impacts on the metastasis of cancer cells remain obscure.
Do prokaryotes have topoisomerase I?
Prokaryotic topoisomerases are present in the cells of prokaryotic cellular origin while eukaryotic topoisomerases are present among organisms with eukaryotic cellular origin.
Do bacteria have topoisomerase?
Discovery. The first DNA topoisomerase was discovered in bacteria by James Wang in 1971 and was initially named ω (omega) protein; it is now called Escherichia coli (E. coli) topoisomerase I (topo I) and is a representative of the type IA family of enzymes.
What is the difference between topoisomerase I and II?
What is the difference between Type 1 and Type 2 topoisomerase?
Type I topoisomerase is an enzyme which changes the degree of supercoiling of DNA by causing single-strand breaks and relegation. Type II topoisomerase is an enzyme which changes the degree of supercoiling of DNA by causing double strands break and relegation.
Are there any inhibitors that target DNA topoisomerases as antibacterial targets?
DNA topoisomerases are key targets for antibacterial and anticancer chemotherapy. TB topo I is validated as an antibacterial target. Inhibitors that target TB topo I have been found.
What do we know about novel bacterial topoisomerase inhibitors (nbtis) against mtgyrase?
Exceptions to this are the naphthoquinone studies described above 59, 60 and work from GSK [72], which identified novel bacterial topoisomerase inhibitors (NBTIs) with activity against Mtgyrase and that lack cross-resistance to fluoroquinolones ( Fig. 5 ).
Is anziaic acid a topoisomerase inhibitor?
Exploring natural product chemical space yielded anziaic acid (Fig. 3) derived from the lichen Hypotrachyna sp. and shown to be a dual inhibitor of type IA as well as type IIA topoisomerases. Anziaic acid was demonstrated to act like a topoisomerase poison.
Is DNA gyrase a potential target for clinical antibiotics?
Although bacterial topoisomerase I has yet to be exploited as a target for clinical antibiotics, DNA gyrase has been extensively targeted, including the highly clinically successful fluoroquinolones, which have been utilized in TB therapy.