Harpers

332 / CHAPTER 36lizing proteins bind cooperatively and stoichiometricallyto the single strands without interfering with the abilitiesof the nucleotides to serve as templates (Figure36–13). In addition to separating the two strands of thedouble helix, there must be an unwinding of the molecule(once every 10 nucleotide pairs) to allow strand separation.This must happen in segments, given the timeduring which DNA replication occurs. There are multiple“swivels” interspersed in the DNA molecules of allorganisms. The swivel function is provided by specificenzymes that introduce “nicks” in one strand of theunwinding double helix, thereby allowing the unwindingprocess to proceed. The nicks are quickly resealedwithout requiring energy input, because of the formationof a high-energy covalent bond between the nickedphosphodiester backbone and the nicking-sealing enzyme.The nicking-resealing enzymes are called DNAtopoisomerases. This process is depicted diagrammaticallyin Figure 36–18 and there compared with theATP-dependent resealing carried out by the DNA ligases.Topoisomerases are also capable of unwinding supercoiledDNA. Supercoiled DNA is a higher-orderedstructure occurring in circular DNA molecules wrappedaround a core, as depicted in Figure 36–19.There exists in one species of animal viruses (retroviruses)a class of enzymes capable of synthesizing a sin-Step 1DNA topoisomerase I = EDNA ligase = EE + ATP E P R A(AMP-Enzyme)5′P -EO 3′H3′ 5′Enzyme (E) -generatedsingle-strand nick5′P3′ 5′O 3′HSingle-strand nickpresentStep 2EEP R A5′P -E5′PP R AOHFormation of highenergybondOHStep 3EP R A(AMP)Nick repairedNick repairedFigure 36–18. Comparison of two types of nick-sealing reactions on DNA. Theseries of reactions at left is catalyzed by DNA topoisomerase I, that at right byDNA ligase; P = phosphate, R = ribose, A = ademine. (Slightly modified and reproduced,with permission, from Lehninger AL: Biochemistry, 2nd ed. Worth, 1975.)