分子生物学-DNA复制

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1、DNAReplicationDNARNAProteinCentraldogmaReplicationReverseTranscriptionTheimportanceofDNAreplicationtomedicineReplicationofthegeneticmaterialisfundamentaltoalllivingthingsErrorsinreplicationaretheoriginofhereditary(genetic)diseasesErrorsinreplicationareusuallytheprimaryorigino

2、fcancersRepliconTheunitofDNAinwhichanindividualactofreplicationoccursiscalledthereplicon.Eachreplicon"fires"onceandonlyonceineachcellcycle.Therepliconisdefinedbyitspossessionofthecontrolelementsneededforreplication.Ithasanoriginatwhichreplicationisinitiated.Itmayalsohaveaterm

3、inusatwhichreplicationstops.DNAstructure:reviewdoublestrandedanti-parallelbasepairingSupercoilingThreebasicrulesofDNAreplicationDNAreplicationissemiconservativeReplicationbeginsatadefinedoriginandusuallyproceedsbidirectionallyDNAsynthesisisinthe5’to3’directionandissemidiscont

4、inuousMostofwhatwewillbediscussingatfirstisDNAreplicationinE.coliOncewehavethegeneralprinciples,wewilldiscussDNAreplicationineukaryotesHowcomplexistheDNAreplicationmachinery?ThemajorplayersDNApolymerases(聚合酶）Primases（引物酶）Ligases（连接酶）Helicases（解链酶）Topoisomerases(拓扑异构酶）Semi-con

5、servative(Messelson&Stahl,1958)DuringreplicationeachoftheoldstrandswillserveasatemplateforthenewstrandsDNAPolymerasesTheycatalyzeatemplate-directedsynthesisofDNAfromnucleotidetriphosphatesAprimerwithafree3’-OHgroupisrequiredSynthesisisinthe5’to3’directionTheyoftenpossess3’to5

6、’exonucleaseactivityBidirectionalWhenarepliconiscircular,thepresenceofDNAreplicationformstheθ-structure.ThesuccessivestagesofreplicationofthecircularDNAarevisualizedbyelectronmicroscopyasshown.OriginsofreplicationInE.colionlyonesiteOriCInman104to105sitesThedirectionofreplicat

7、ionisbidirectionalOriCOriCOriCThestructureofOriCConsensussequenceoftheminimalbacterialreplicationoriginbasedonanalysesofgenomesfromsixbacterialspeciesDNAreplicationandcelldivisioninaprokaryoteHowisreplicationinitiated?DnaAproteinbindsto9-mersandinitiatesreplicationDnaAtogethe

8、rwithHUdenaturetheDNADnaBhelicasebindstheopenDNA(DnaA…X发现于细菌，与复制有关的一