諾貝爾專題PPT課件

1、第1頁/共26頁The2009NobelPrizeinPhysiologyorMedicineisawardedtoDrs.ElizabethHBlackburn,JackWSzostakandCarolWGreiderfortheirdiscoveryofhowchromosomesareprotectedbytelomeresandtheenzymetelomerase.第2頁/共26頁Figure1.Theend replicationproblem第3頁/共26頁thestageforthediscoveriesThepresenceofDNArepeatsnearorattheend

2、soflineareukaryoticchromosomeshadbeenrecognizebytheearly1970s,butdetailedendsequenceinformationdidnotbecomeavailableuntil1978.UsingtheunicellularciliateTetrahymenathermophilaasamodelorganismJosephGallfoundthattheamplifiedrDNAwaspresentaslinearDNA.ElizabethBlackburnsetouttodeterminetheendsequenceofth

3、erDNAMolecules.TheresultsshowedthattherDNAmoleculescontainedtandemrepeatsofthehexanucleotideCCCCAAateachend.Inadditionitwasnotedthatthenumberofrepeatsvariedbetween20and70.第4頁/共26頁JackSzostakfoundthattheendsoflinearplasmidDNAmoleculesintroducedintoyeastcellswerehighlyrecombinogenic,promotingrearrange

4、mentorinteractionwithhomologouschromosomalDNAandintegration,andlongtermmaintenancewasnotpossible第5頁/共26頁AcrucialstepwasinitiatedwhenElizabethBlackburnandJackSzostakattendedthesameGordonConferencein1980.TheydecidedtocollaboratetoinvestigateifaddingTetrahymenachromosomeendrepeatDNAsequencestolinearyea

5、stplasmidscouldstabilizetheendstoallowreplication.第6頁/共26頁Figure2TheDNAend sequenceoflinearDNAmoleculesfromTetrahymenaaddedtoartificialminichromosomesallowstheirlongtermstablemaintenanceinyeast.第7頁/共26頁Akeyconclusionemergingfromtheseexperimentswasthatthestrikingandevolutionarilyconservedfunctionalpr

6、opertiesoftheTetrahymenarDNAendsequencesprovidedchromosomalstability.This,combinedwiththepresenceoffunctionallysimilarsequencesinyeastallowedthedeductionthatsuchendsequencescorrespondedtofunctionaltelomeres.第8頁/共26頁InafollowingstudyGreiderandBlackburnshowedtheenzymetobeaRNPcomplexcriticallydependent

7、onboththeproteinandRNAcomponent第9頁/共26頁AtthispointthesalientkeyfeaturesofthetelomeraseenzymeasauniquetypeofreversetranscriptasewithacatalyticproteincomponentandanintrinsicRNAtemplatehadbeenelucidated.Thebasicmechanisoftelomeresynthesisandmaintenancewasthusestablished.第10頁/共26頁Figure3.Modelforelongat

8、ionoftelomeresbytelomerase.第11頁/共26頁Significanceofthediscoveryoftelomerefunctionandtelomerase Cancer Ageing Stemcellmaintenance Hereditarydiseasesyndromes第12頁/共26頁ThediscoveriesconcerningtelomerefunctionandmaintenancethatarerecognizedbythisyearsNobelPrizeinPhysiologyorMedicinehavesolvedoneofthefunda

9、mentalproblemsinbiologyandopenedawholenewresearchfield.第13頁/共26頁第14頁/共26頁ThisyearsNobelPrizeinChemistryisawardedtoVenkatraman*Ramakrishnan,ThomasA.SteitzandAdaE.Yonathfortheirstudiesofthestructureandfunctionoftheribosome.第15頁/共26頁anorganismspropertiesarehereditaryandthat,everynowandthen,randomchange

10、soccur.Successfulchanges,whichincreasethechancesofsurvivaloftheorganisminquestion,arethuscarriedforwardtofuturegenerations.第16頁/共26頁somenewquestionsarose:whatexactlyisbeingtransferredovergenerations,wheredotherandomchangesoccur,andhowcantheymanifestthemselvesinalivingorganism?第17頁/共26頁第18頁/共26頁Figur

11、e4.X-raycrystallographyshowsthestructureofribosometheproteinsofthesmallsubunitareblueandtheproteinsofthelargesubunitaregreen.第19頁/共26頁第20頁/共26頁第21頁/共26頁Figure4.Thepathtothe50SsubunitstructureathighresolutionThe50Ssubunitstructureat9resolution(left,1998),5resolution(middle,1999)and2.4resolution(right

12、,2000).第22頁/共26頁Figure7.Themechanismofpeptidebondformationontheribosome.The-aminogroupofaminoacyl-tRNAintheAsite(blue)attacks(blackarrowrighttoleft)theesterbondofthepeptidyl-tRNAinthePsite(red).AprotonisshuttledviatheOHgroupofA76inpeptidyl-tRNAinthePsite(blackarrowslefttoright),aidedbyanH-bondnetwork(Trobroandqvist,2005)establishedwiththehelpof23SrRNAbasesandwatermolecules(notshown).第23頁/共26頁Figure8.Thepeptidyl-transferasecenterinthe50Sribosomalsubunitisattackedbyalargenumberofexistingantibiotics第24頁/共26頁Theunderstandingoftheribosomesstructureandfunctionisofgreatandimmediat