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1、氟罗沙星能潜在干扰Bloom解旋酶的DNA解链、ATP酶、DNA结合活性 Potent interference of DNA unwinding ATPase and5101520DNA-binding activities of Bloom helicase by FleroxacinLUO Heng123 XU Houqiang12 CHEN Xiang12 DING Mei12 YANG Qixin12XU Qinghe12 LIU Jinhe12 1 Key Laboratory of Animal GeneticsBreeding and Reproduction in the P
2、lateau MountainousRegionMinistry of EducationCollege of animal scienceGuizhou University GuiYang 5500252 Guizhou Key Laboratory of Animal Genetics Breeding and Reproduction College of animalscience Guizhou University GuiYang 5500253 The Provincial Key Laboratory for Agricultural Pest Management of M
3、ountainous RegionGuizhou University GuiYang 550025 Abstract Bloom BLM helicase plays an important role in the processes of DNA metabolismincluding DNA replication repair transcription and recombination Fleroxacin FLRX an importantantibiotic applied in the empirical treatment of a variety of infectio
4、ns has currently been used as theeffective drugs for anti-cancer therapy This study was conducted to determine the effects of FLRX onthe biological properties of BLM helicase catalytic core by fluorescence polarization spectroscopyfree-phosphorus assay and gel retardation assay Results indicated tha
5、t the DNA unwinding andATPase activities were inhibited by FLRX treatment However the DNA-binding activity waspromoted BLM-FLRX complex was form through one binding site electrostatic force andhydrophobic interaction force Moreover the intrinsic fluorescence of the helicase was staticallyquenched by
6、 FLRX as a result of non-radioactive energy transfer The results suggested that FLRXmay affect the biological activities and conformation of the BLM helicase which were beneficial tostudy the efficacy of DNA helicase as the target of drugsKeywords BLM helicase fleroxacin biological activity250 Intro
7、ductionAs an important member of highly conserved DNA helicases from bacteria to humans TheRecQ helicases family performs several essential roles in genetic recombination transcriptionDNA replication and DNA repair 1-2 Human RecQ helicases such as BLM and WRN play a303540key role in chromosomal main
8、tenance and their defects have been shown to associate withBlooms syndrome cancer predisposition and Werner syndrome premature aging predisposition 3-4 BLM helicase of RecQ family of helicases 5-6 Previous studies have shown that the RecQ coreof BLM helicase the amino acid residues 642-1290 displays
9、 similar enzymatic properties as thefull-size BLM helicase 7 As the unique and important roles of human RecQ helicases in genomicstability a number of strategies currently have been explored to combat many types of cancerthrough modulating the functions of human RecQ helicases or interaction factors
10、 8-10 Multipleevidences indicated that human RecQ helicases may be suitably as the target of cancerstherapeutic 8-9 Many small molecule drugs have been proved that is an efficient approach forcancers treatment by modulating the expression level or function of RecQ helicase 11 In additionthe abnormal
11、 cancer cells were selectively regulated through inactivating the helicase-dependentDNA metabolism pathways including DNA recombination replication repair and cell cyclecheckpoint 12-13Foundations The authors are grateful for financial support from National Basic Research Program of China No2010CB53
12、4912 the Doctoral Program of the Ministry of Education No200806570003 the Governor ofGuizhou Province Talents Fund No200822 and Guizhou University innovation funds of graduate student NoSYN 2009005 Brief author introductionLUO Heng 1985- male PhD Students Molecular Biology of the CellCorrespondance
13、author XU Houqiang 1957- male professor Molecular Biology of the Cell E-mailhouqiang0524yahoocom-1-Fleroxacin FLRX Fig1 is an important antibiotic in a class of drugs called45505560657075fluoroquinolone has been applied in the empirical treatments of a variety of infectionsparticularly in those of g
14、enitourinary gastrointestinal and respiratory tracts 14 The study hasdemonstrated that fluoroquinolone administered for therapy of some cancer for example BladderCancer 15 indicating that fluoroquinolone may be as the effective drugs for cancer treatment Themechanism of action of the fluoroquinolone
15、 has been demonstrated that it may affect the activityof many related enzymes to regulate DNA and energy metabolism of cell 16-18 The study showedthat fleroxacin can affect the structure and functions of topoisomerases such as topoisomerase II DNA gyrase topoisomerase III and topoisomerase IV which will be helpful to control theabnormal cells of the diseases by interference of the DNA metabolism 19-20Fig1 The chemical structure of FLRXBLM helicase is associated with topoisomerase III TEP1 telomerase-associated protein 1 HSP90 heat shock protein 90 and t
