MODELS OF REPLICATION

Replication models

1. K. Narayanapura, Kothanur (PO), Bengaluru 560077
Tel[phone] Fax. [phone]
e-mail:[email protected], www.kristujayanti.edu.in
MODELS OF REPLICATION
Dr.Manikandan Kathirvel
Assistant Professor,
Department of Life Sciences,
Kristu Jayanti College (Autonomous),
Bengaluru

2. Model of replication
■Eachchainofdoublehelixactsastemplateandis
evolvedinreplicationofDNA.
■WatsonandCrickproposedthatthehydrogen
bondsbetweenthebasepairsoftwostrandsare
brokenandseparatedfromeachother.
■Eachpurineandpyrimidinebaseofthestrands
formshydrogenbondswithcomplementaryfree
nucleotidestobeinvolvedinpolymerizationinthe
cell.
■Thefreenucleotidesformphosphodiesterbonds
withdeoxyriboseresidueresultinginformationofa
newpolynucleotidemolecule.
■ThismodelofWatsonandCrickforDNAreplication
waslateronverifiedexperimentally.
OneofthemostimportantpropertiesofDNAfunctioning
asthegeneticmaterialisthatitcanmakeexactcopiesof
itself(autocatalyticfunction)formingthebasisfor
transmissionofhereditarycharactersitcontrols.
Thisprocessiscalledreplication.

3. MODELS 0F REPLICATION
■1.ASYMMETRIC REPLICATION
■2.ROLLING CIRCLE MODEL
■3.D-LOOP MODEL
CONCATEMER FORMATION

4. TheleadingstrandandlaggingstrandthatareunwoundbytheDNAhelicaseatthereplicationfork
runinoppositedirections,butthenewDNAsequencesaresynthesizedinonlyonedirection,i.e.,5’
to3’direction,becausetheenzymesinvolvedinDNAreplicationcanonlyworkinthe5’to3’
direction.
Therefore,thesetwotemplatestrandsarereplicatedindifferentways,resultingintheasymmetryof
DNAreplication.
DuringDNAreplication,theleadingstrandcanbecontinuouslyreplicatedbythepolymerasesinceits
templatestrandisinthe3’to5’direction.
However,thereplicationofthelaggingstandisnotsostraightforward.Itcannotbecreatedina
continuousmannerduetothe5’to3’directionalityofitstemplatestrand.Polymerasesneedtowork
backwardsfromthereplicationfork,creatingperiodicbreaksintheprocessofreplicatingthelagging
strand.DNAfragments,ratherthancontinuousDNAsequenceasintheleadingstrand,are
generatedinthelaggingstrand.Thesefragments,knownasOkazakifragments,arethenconnected
intoasingle,continuousstrandbytheDNAligase.Inthisway,theentirereplicationprocessis
completedanditisconsideredasymmetricbecauseofthedifferenceinreplicatingthesetwostrands.
I). ASYMMETRIC REPLICATION

5. I). ASYMMETRIC REPLICATION
■ThesequencesofthetwostrandsofaDNAmoleculerunin
oppositedirections,butduringreplicationthenewDNA
moleculesaresynthesizedinonlyonedirection,because
theenzymesinvolvedinDNAreplicationcanonlyworkin
the5’to3’direction.
■Eachstrandisthereforeduplicateddifferently.
■Theleadingstrandisusedasatemplatebyapolymerase
enzyme(Polε),whichmakesanewmoleculeina
continuousmanner.
■Bycontrast,duplicationofthelaggingstrandisdiscontinuous
andrequiresanotherpolymerase(Polδ),whichsynthesizes
shortDNApiecesknownasOkazakifragments.
■Theseokazakifragmentsarethenjoinedtogetherwiththe
helpofotherenzymestoformacontinuousmolecule.
■Duringtheprocess,nucleosomes-proteincomplexesaround
whichDNAiscoiled-disassemblefromparentalDNAtothen
reassemble,alongwithadditionalnucleosomeproteinsas
needed,allowingbothDNAduplicationandchromatin
reorganization.

6. II). D-LOOPED MODEL
Thismodeofreplicationoccursinmammalianmitochondriaand
Chloroplast
Themitochondrialchromosomeincircular.Onestrandofthe
chromosomeisdenotedasHstrand,whileitscomplementary
strandisnamedLstrand.
■Replicationbeginsataspecificorigin,butonlyonestrand,the
Hstrand,isreplicated;theotherstrand(theLstrand)ofthe
chromosomeisdisplacedformingaloop,calleddisplacement
looporDloop.
■Whenreplicationof(theHstrand)hasprogresseduptoabout
2/3ofthechromosome,thereplicationofthedisplacedsingle
strand(Lstrand)begins.
■Thisreplicationbeginsatadifferentoriginandreplication
proceedsintheoppositedirection.
■ThusboththestrandsofDNAarereplicatedinacontinuous
manner,theirreplicationsbeginatdifferentorigins,and
replicationofonestrand(Hstrand)beginsmuchearlierthanthat
oftheother(Lstrand).
■Inthiscase,replicationisnotonlyunidirectional,butthe
replicationofonlyoneofthetwostrandstakesplaceateachof
thereplicationforks

7. III). ROLLING CIRCLE MODEL
■Rollingcirclereplicationisaprocesswhichacircular
DNAorRNAmoleculeisreplicatedinonedirection.
■Thisparticularprocessoccursinplasmidandvirus’s
genome.
■TheprocessofDNAisinitiatedbyinitiatorprotein
whichnicksatthesitecalledthedouble-strandedorigin
ononestrandofthedouble-strand.
■Theinitiatorproteinremainsonthe5’phosphatenick
strand,andthe3’hydroxylendofthenickedstrandis
elongatedbyDNApolymeraseIII.
■Theunnickedstrandactsasthetemplatestrandfor
replicationandthe5’phosphatenickstrandisdisplaceby
helicase.
■Eventually,thenickstrandiscompletelydisplacedby
newlysynthesisedstrandandwillremoveitselffromthe
originalcircularDNAbythesameinitiatorproteinnicking
attheterminatingsequenceonthenickedstrand.
■Thenickedstrandthenformanewsingle-stranded
circularDNAmolecule.RNApolymeraseandDNA
polymeraseIIIthenusethesinglestrandasatemplateto
formnewdouble-strandedcircularDNAmolecule.

8. AconcatemerisalongcontinuousDNAmoleculethatcontainsmultiplecopiesofthe
sameDNAsequencelinkedinseries.
Thesepolymericmoleculesareusuallycopiesofanentiregenomelinkedendtoendand
separatedbycossites(aproteinbindingnucleotidesequencethatoccursonceineach
copyofthegenome).
Concatemersarefrequentlytheresultofrollingcirclereplication,andmaybeseeninthe
latestageofbacterialinfectionbyphages.
Asanexample,ifthegenesinthephageDNAarearrangedABC,theninaconcatemer
thegeneswouldbeABCABCABCABC andsoon(assumingsynthesiswasinitiated
betweengenesCandA).Theyarefurtherbrokenbyribozymes.
Duringactiveinfection,somespeciesofviruseshavebeenshowntoreplicatetheir
geneticmaterialviatheformationofconcatemers.Inthecaseofhumanherpesvirus-6,its
entiregenomeismadeoverandoveronasinglestrand.Theselongconcatemersare
subsequentlycleavedbetweenthepac-1andpac-2regionsbyribozymes,whenthe
genomeispackagedintoindividualvirions.
Concatemer