诺贝尔专题PPT课件

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

2、soflineareukaryoticchromosomeshadbeenrecognizebytheearly1970s,butdetailedendsequenceinformationdidnotbecomeavailableuntil1978.UsingtheunicellularciliateTetrahymenathermophilaasamodelorganismJosephGallfoundthattheamplifiedrDNAwaspresentaslinearDNA.ElizabethBlackburnsetouttodeterminetheendsequenceofth

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

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

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

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

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

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

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

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

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

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