北大生物化学完整课件chapter7.pptx

北大生物化学完整课件chapter7.pptx

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NucleotidesDeoxyribonucleicAcids（DNA）RibonucleicAcids（RNA）DaochunKongTheCollegeofLifeSciencesPekingUniversityDeoxyribonucleicAcids（DNA）In1868,FriedrichMiescher,aSwissbiologist,isolatedaphosphorus-containingsubstancefromthenucleiofpuscells（leukocytes）,whichhecalled“nuclein”.Hefurtherfoundthatthe“nuclein”consistedoftwoportions.Oneportionisacidic,whichwenowknowasDNA.Theotherportionisbasic,whicharemostlyhistoneproteins.Thereofre,the“nuclein”Miescherisolatedwasactuallychromatin.Later,hefoundthatasimilarsubstanceintheheadsofsalmonspermcells.1.TheDiscovery:

2.DNA,theGeneticSubstance:

1）.DNAwassuspectedtobegeneticmaterial,but,therewasmorereasontoassignthisroletoproteins.Proteinswerethoughttobelarger,morecomplex（composedoftwentydifferentaminoacids）,andthereforeweremoresuitableforageneticrole.DNAwasthoughttobejustarepeatingpolymerofonekindoftetranucleotideunit.Itwasjustaboutseventyyearsago,in1930s,DNAwaswidelybelievedtoexistonlyinanimalcells,andRNAwasinplantcells.Plantandanimalcellsweresometimesdistinguishedbasedonthischemicalfeature.2）.In1928,FrederickGriffithdiscoveredthephenomenonoftransformationinbacteriaStreptococcuspneumoniaehastwoforms,Slimycolonies（virulentSstrain）formsmucouscapsules,itkillsmice.But,heat-killedstraindoesnotkillmice.Roughcolonies（non-virulentRstrain）lackscapsules,itdoesnotkillmice.Mixedheat-killedS-strainwithliveR-strain,resultingorganismskilledmice.Conclusion:

somechemicalincellsofSstrainisstableinheattreatment,retainsgeneticinformation,isabletotransmitthatinformationtoR-strainbacteria,convertthemtoS.3）.In1944,Avery,MacLeod,andMcCartyfoundthatDNApreparedfromavirulentstrainofpneumococcuscouldtransformanonvirulentstrainofthisorganismintoavirulentone.VirulentbacteriaInjectionMousediesNonvirulentbacteriaMouselivesAveryOT,MacLeodCM,McCartyM（1944）J.Exp.Med.79:

137.NonvirulentbacteriaDNAfromvirulentbacteriaDNAcarriedageneticmessagefromonetypeofcellscouldbeassimilatedandexpressedbyanothertypeofcells.Conclusion:

Argument:

Atthattime,noteveryoneacceptedAveryetalsconclusion.Thecriticsattackedthat,a.TheDNAwaspossiblycontaminatedbyslightamountofproteinsthatwasresponsiblefortheobservedtransformation.b.DNAmaybegeneticsubstancejustinbacteria.Whatareyourexperimentstoeaseoreliminatethesecriticsdoubts?

4）.In1952,AlfredD.HersheyandMarthaChasediscoveredthatitwasbacteriophageT2DNAthatenteredhostcell,E.coli,andcarriedgeneticinformationforphagereplication.Atthattime,itwasalreadyknown,a.BacteriophagecontainsonlyDNAandproteins.b.PhageproteinsdonothavephosphorusP,butdocontainsulfurSinaminoacids.DNAdoesnothaveS,butlotsofP.HersheyandChasesexperiment5）.In1953,WatsonandCrick,basedonexperimentalevidencesprovidedbytheotherpeople,suggestedamodelforstructureofDNA-acomplementary,doublestranded,andhelicalstructureofDNA.Thismodelwasprovedcorrectseveralyearslater.Basedontheaboveandotherstudies,itisfinallydemonstratedthatDNAisindeedgeneticsubstance.Ithastwodiscretefunctions-Oneistocarrygeneticinformationthatbringsaboutthespecificphenotypeofthecell;Anotherisitsownreplication.1.Howmanykindsofnucleicacids?

2.Chemicalconstituentsofnucleicacids3.Structureofnucleicacids?

4.Chemicalpropertiesofnucleicacids?

3.ChemistryofNucleicAcidsTwoKindsofNucleicAcidsinAllOrganisms1.DNA-Deoxyribonucleicacids2.RNA-Ribonucleicacids1.DNAisalonglinearpolymercomposedoffourkindsofmonomerunitscalleddeoxyribonucleotides（A,G,T,C）linkedtoeachotherinachain.DNA5-AGTCCCTAGGACTATTTAAAACCTGGAGAGT-32.Single-strandedDNA（ssDNA）anddouble-strandedDNA（dsDNA）.Innature,mostofDNAisintheformofdsDNA.RNA1.RNAisalsolinearpolymerscomposedoffourtypesofribonucleotides（A,G,C,U）.5AGCUAAGUCCUUUGGGAACCCAAGGUUAACC32.RibosomalRNAs（rRNA）MessengerRNAs（mRNAs）TransferRNAs（tRNAs）andOtherRNAmoleculesChemicalStructureofNucleotidesAlexanderR.Todd（1954）chemicalstructureofthenucleicacids.PNAS.40:

748-755DifferencesofNucleotidesbetweenDNAandRNADeoxyadenylateDeoxyguanylateDeoxythymidylateDeoxycytidylateDeoxyribonucleotidesAdenylateGuanylateUridylateCytidylateRibonucleotidesSomeRareBasesinDNAandRNA5-MethylcytidineN6-MethyladenosineN2-Methyladenosine5-HydromethylcytidineInosinePseudouridine7-Methylguanosine4-ThiouridineRarebasesinDNARarebasesinRNADNARNADNA&RNAPolymerIndividualnucleosidesarejoinedtogetherbyphospho-diesterbonds,notetherorpyrophosphatelinkages.Levene&Simms（1925,1927）JBC.65:

519;70:

327.4.StructureofDNAErwinChargaff1）.ErwinChargaffmeasuredamountsoffournucleotidesinDNAfromdifferentorganismsCompositionsofdeoxyribonucleotidesinS