DNA topoisomerases: organizer of genome

DNA topoisomerases: organizer of genome :
It can be readily observed from above discussion that themajor trick in genome organization is to coil and supercoil DNA around histone backbones followed by further supercoiling of the repeat units. Following the topological property, supercoiling in positive or negative directions creates writhe in DNA, thereby
inducing torsional stress. To stabilize DNA at this position as well as to relieve torsional stress, linking number of DNA molecule has to be changed, which can only be achieved by breaking phosphodiester bond and rotating the strands of the helix. The enzymes that perform this cellular duty are known as DNA
topoisomerases. Topoisomerases are essential not only in genome organization, but are indispensable components of replication, transcription, recombination and DNA repair, each of which requires localized unfolding and refolding of DNA in a precise manner without entangling of DNA loops plus no interference
in the structural organization of adjoining genomic regions.
     All the topoisomerases breaks and rejoins DNA strands. There are two general types, type I and type II topoisornerases which differ in their properties of cleaving DNA. Type I topoisomerases (Topo I) deave single strand and do not require additional energy to perform the action. Type II. on the other hand break double strands and require ATP for this function. A tvrosine residue in the active site of topoisomerase I targets and breaks phosphodiester bond by forming linkage of hydroxyl group of tyrosine and 5’phosphaLe of DNA at the breakpoint. The second strand, which is held by the enzyme, is then passed through the gap created to reduce the linking number by one. In case of type II topoisomerases (Topo II), which cleave both
strands and pass one through the other, linking number is changed by two in each reaction. Type II enzymes bind to DNA as a molecular clamp, bind to a region called G segment. A pair of tvrosine residues of N terminal end of the enzyme then attacks both the strands. The protein clamp forms dimer in presence of
ATP which allows strand passage. If both strands are from same DNA, then the duplex is relaxed. If the strands are from different DNA molecules, catenation or decatenation is observed.
         Topo I can be further classified in two suhfamilies. The first group (Type IA) includes bacterial topo I and III, and eukaryotic topo HI, which join to the 5’ phosphate group. Type lB contains eukaryotic nuclear topo I that targets 3’ phosphate end. Reverse gvrase, another type I enzyme observed in prokaryotes is unique in the sense that it can introduce positive supercoil in DNA. Although it is a type I enzyme, it requires AT!’ for introducing positive supercoiling. The enzyme also functions to protect DNA breakage at high temperature, as many bacteria having reversen gyrase have very high optimum growth temperature.
        In higher eukaryotes, two types of type IL topoisomerase, alpha and beta isomers exist which are homodimeric proteins encoded by a single gene. Beta form is preferentially associated with nucleolus. A special type 11 topoisomerase namely DNA gyrase is present in bacteria, which can introduce negative
supercoil in DNA strands. DNA gyrase is a heterotetramer comprising of two gyrase A and gyrase B proteins each (A2B2), while eukaryotic type II topoisomerases are homodirners. Ability of gyrase to introduce negative supercoil lies in wrapping of 1are DNA region compared to other type II enzymes and dictating the orientation of the transported segment during strand passage while forming a tyrosine- phosphate dimer linkage.