Chapter 6 DNA Replication & Repair PDF

CHAPTER 6 DNA Replication Repair DNAReplication the differencesbetween titi I iii IIIiterate.ie milme a FEEitiiaImeat nes.in esisotnewstranaauringmarer DNAreplication is sem...

CHAPTER 6 DNA Replication Repair DNAReplication the differencesbetween titi I iii IIIiterate.ie milme a FEEitiiaImeat nes.in esisotnewstranaauringmarer DNAreplication is semiconservative becauseeachdaughterDNAhelixiscomposedof 1 old conserved 1 new DNAsynthesisbegins at Replicationorigins DNAhelixnormallystable heldbymanyhydrogenbonds onlyboilingH2OcanbreakH H ButtemplateDNAmustbe first openedup 2strandsseparatedHow Processbeginswithinitiatorproteins thatbindtoORItobreakhydrogenbonds AlthoughhydrogenbondsmakeDNAstableindividuallytheyRwe Initiator proteins canunzipshortregionsofdoublehelix norm.tem Hypstands DNA sequences at ORIrecognized byinitiatorproteins Nature of Replication 3 models for DNAreplication semiconservative eachparentstrandservesas atemplateforsynthesis disperse nissa ÉpiiÉnfÉnewly synthesizedDNA mix SYasstkhkntettnetwmetdf.ie intactafterbeingcopied  Melson StaniExperiments to confirmmodel ofDNARep BacteriagrownonisotopecontainingmediatolabelDNA Cells arebroken DNAisloadedintoultracentrifugetubecontainingcesiumchloridesaltsol tubescentrifuged athighspeedstoformgradient AsgradientformsDNAmigratestoregionwheredensitymatchessurroundingof salt Heavy lightDNAmoleculescollect in diff positionswithinthetube HeavyisotopeN'swasdenser gradientclosertobottomoftube 2 Theythen testedsamehypothesis withE coli Rohellaneetmode generationwas 199 9 91stents p resuting dispersivemotel wnithbky.FItonas TwoReplicationForks Form at each Replication Origin DNAsynthesisoccurs atY shapedjunctionscalled replicationforkswhichmoveawayfrom eachother as they unzip doublestrand inoppositedirections unzipping 2 O Bidirectional morerapidly Phyllida whatplayers are involvedin DNAsynthesis DNApolymerase DNApolymerase synthesizes DNAusinga ParentStrand as aTemplate DNAsynthesisin 5 to3 directioneverynucleotidepairisaddedto3endofnewstrand nucleoside base sugar r nucleotide with 21 phosphategrow nuclei acid longchainsof withgene.fi DNApolymerase catalyzes additionof nucleotides to growing3 end Pglymperizationreactioninvolves formationofphosphodiesterbondbetween3 end 5 phosphat  when deoxyribonucleosidetriphosphate phospho entersrealtion phosphate cleaves OH Feleasing 2 P'groups results in pyrophosphate hydrolysis furtherhydrolyzed to makespolymerizationirreversibl DNApolymerase catalyzesreaction guidesnucleoside triphosphate properbasepairingallows5 triphosphate toreact with3 0H on growingstrand ask.es oYEtaa5aiFoi'o uYieotides duringDnasynthesis The ReplicationFork isAsymmetrical ininertia rain's middlestrand matinitical DNApolymerase3 readstemplate 3 5 direction BUTwrites5 3 direction Leading strand newly synthesizedDNA strand that iscontinuously in 5 3 direction LeadingstrandTemplate templatestrandthatguidesthesynthesisof leadingstrandruns3 5dire Allnewly synthesizedstrandsare eitherleadingorlaggingdependingondirectionrelativetorepfork DNAPolymerase is Self correcting ProofreadingoccurswhenDNApolymerasemakesmistake addswrongnucleotide Proofreadingcorrectserror occurssimultaneously withDNAsynthesis DNA Polymerase 3 containsseparatesitesfor DNAsynthesis Proofreading P polymerizing can ur E editingproofreading 8,1 whenpolymeraseaddsincorrectnucleotide red strand new unpairstemporarily movesto E site to becorrected Howdoesreplicationbegin at origin of replication ShortRNA'sactprim O knownasprimersessentialforDNArep starting provide jointforpolyimmerdale to addnucleotides RNAprimersare complementarytosinglestrandedDNAtemplate nonceDNAsynthesisproceedsRNAreplacedbyDNA primasesynthesizesRNAusingDNAas template Multiple Enzymes are required to synthesizelagging DNAstrand RNAprimers 10nucleotides extended by DNApolymerase to formokazakifragments RNAprimersremovedby nucleasesthatdegradeRNAstrand Gapsleft arefilledbyDNA polymerase 1 DNAligasejoins DNAfragmentsbyformingphosphodiesterbonds Ligationprocess requires ATP toprovide the energyfortherx DNA Ligase joins together Okazaki fragments on laggingstrand during DNA synthesis via ATPhydrolysis adenine monophosphate  ligase enzyme uses molecule of ATP to activate 5 phosphate to bond with 3 OH Telomerase replicates theends of Eukaryotic Chromosomes DNAreplicationrisks losing chromosomeends replicationstarts at origins continues to chromosome ends leading strand is fullysynthesized lagging strand can't becompleteddueto removalof finalRNAprimer HowdoesDNAreplicationpreventlosingits end telomerasepreventschromosome end shrinkage duringcelldivision Telomerase prevent linear Eukaryotic chromosomes fromshortening Telomeraseextends the templatestrand beyond the DNAto be copied Theextendedtemplate allowsprimaseto lay downRNAprimers Telomerase uses RNA as a template to synthesize telomereDNA Afterreplication the lagging strandiscompletemaintaininggenetic info Telomere lengthvaries b ycelltype with Ag TalmmagesqhrehftnihnefImtsenggnew.tn threenngm8stms.romosomes that protectthemfrom They aresometimescompared to the plastictips at the ends of shoelaceslaglets as theyhelpmaintainintegrityofchromosome Variation by cell type Differenttypesofcellshavevaryingtelomere lengths due todifferences in their rate of division thepurposetheyserve in thebody ForEX Stemcells germcellstendtomaintain longertelomeresbecausethey needto divide extensively remainfunctional over a lifetime Somaticcells have shortertelomeresbecausetheydividefewertimesHowever with eachdivision smallportion of telomere is lost DNA Repair DNA Damageoccurs continually in cells Depurination Deamination are the mostfrequentchemicalreactions knowntocreate seriousDNAdamage in cells Depurination process that removes guanine or adenine fromDNAleading to possiblemutation Deamination conversionof cytosine to uracil an abnormalbase in DNA otherbasescan alsoundergo deamination Imact on DNA Bothcan altergeneticcodewithoutbreaking phosphodiesterbackbone Consequences Thesemodificationscanlead to errorsduringDNAreplication repair mutations DNAIntegrity Reactionsare common sourcesofDNAdamagethoughtheydon'tdisruptstructu integrity of the DNAhelix Ultravioletradiationinsunlightcancauseformation of ThymineDimers promotescovalent linkagebetween 2 adjacentpyrimadinebasesformingdimer  can cause xeroderma pigmentosum Chemicalmodifications of nucleotides if left unrepaired producepermanentmut cells possess a variety of Mechanisms for Repairing DNA 3Steps for Repairing DNA 1 Segment of Damaged strand isexcised aka extision 2 RepairDNApolymerasefills in missingnucleotide intopstrandusingbottomstrand as template aka resynthesis 3 DNAligasesealsnick aka ligation A DNA Mismatch Repair System Removes Replication Errors that Escape Proofreading Mismatchrepair dedicatedto correctingerrors corrects 99 of reperrors mispaired nucleotide is called a mismatch If leftuncorrected permanentmutation prevalentincancerpredisposition Permanent mismatch repair mutation proteins restore seq Doublestrand DNA breaks Require a Differentstrategyfor Repair Cells can repairdoublebreaks in 2ways NonhomologousEndjoining rapidstickingofDNA brokenfragmentsback togetherbefore theydriftapart getlost Aka quick dirty but nucleotides lost at site ofrepair Homologous Recombinationflawlessrepair ofdoublestrandbreakwithnoloss of geneticinfo by a recombination specificnuclease chewsback5 endsof brokenstrands specializedenzym treca bact Rad52 euk one of broken3endsinvadesunbrokenDNA looksforcomplim Homologous Recombination can Flawlessly RepairDNADoubleSt Failure to RepairDNADamage can Have severe consequences for a cell or organism Glutamicacid gets replaced by valine