NucleicAcids

Nucleicacidsaremoleculesthatstoreinformationforcellulargrowthand
reproduction
Therearetwotypesofnucleicacids:
deoxyribonucleicacid(DNA)andribonucleicacid(RNA)
Thesearepolymersconsistingoflongchainsofmonomerscalled
nucleotides.Anucleotideconsistsofanitrogenousbase,apentosesugar
andaphosphategroup:

TheCentralDogma(F.Crick):

DNAmRNAProtein
(genome)(transcriptome) (proteome)

Themonomericunitsfornucleicacidsarenucleotides
Nucleotidesaremadeupofthreestructuralsubunits
1.Sugar:riboseinRNA,2deoxyriboseinDNA
2.Heterocyclicbase
Nucleosides,Nucleotides,andNucleicAcids.
Nucleicacidsarethethirdclassofbiopolymers(polysaccharides
andproteinsbeingtheothers)
Twomajorclassesofnucleicacids
deoxyribonucleicacid(DNA):carrierofgeneticinformation
ribonucleicacid(RNA):anintermediateintheexpression
ofgeneticinformationandotherdiverseroles
TheCentralDogma(F.Crick):

DNAmRNAProtein
(genome)(transcriptome) (proteome)

Themonomericunitsfornucleicacidsarenucleotides
Nucleotidesaremadeupofthreestructuralsubunits
1.Sugar:riboseinRNA,2deoxyriboseinDNA
2.Heterocyclicbase
3.Phosphate
2
Nucleoside,nucleotidesandnucleicacids
phosphate

sugar base

phosphate phosphate

sugar base
sugar base sugar base

phosphate
nucleoside nucleotides
sugar base

nucleicacids

Thechemicallinkagebetweenmonomerunitsinnucleicacids
isaphosphodiester 3
 NitrogenBases
Thenitrogenbasesinnucleotidesconsistoftwogeneraltypes:
purines:adenine(A)andguanine(G)
pyrimidines:cytosine(C),thymine(T)andUracil(U)
 PentoseSugars
Therearetworelatedpentosesugars:
RNAcontainsribose
DNAcontainsdeoxyribose
Thesugarshavetheircarbonatomsnumberedwithprimes
todistinguishthemfromthenitrogenbases
 NucleosidesandNucleotides
Anucleosideconsistsofanitrogenbaselinkedbyaglycosidic
bondtoC1ofariboseordeoxyribose
Nucleosidesarenamedbychangingthethenitrogenbase
endingtoosineforpurinesandidineforpyrimidines
Anucleotideisanucleosidethatformsaphosphateesterwith
theC5OHgroupofriboseordeoxyribose
Nucleotidesarenamedusingthenameofthenucleoside
followedby5monophosphate
NamesofNucleosidesandNucleotides
 AMP,ADPandATP
Additionalphosphategroupscanbeaddedtothenucleoside5
monophosphatestoformdiphosphatesandtriphosphates
ATPisthemajorenergysourceforcellularactivity
 PrimaryStructureofNucleicAcids
Theprimarystructureofanucleicacidisthenucleotidesequence
Thenucleotidesinnucleicacidsarejoinedbyphosphodiesterbonds
The3OHgroupofthesugarinonenucleotideformsanesterbond
tothephosphategrouponthe5carbonofthesugarofthenext
nucleotide
 ReadingPrimaryStructure

Anucleicacidpolymerhasafree
5phosphategroupatoneendanda
free3OHgroupattheotherend
Thesequenceisreadfromthefree
5endusingthelettersofthebases
Thisexamplereads
5ACGT3
 ExampleofRNAPrimaryStructure
InRNA,A,C,G,andUarelinkedby35esterbonds
betweenriboseandphosphate
 ExampleofDNAPrimaryStructure
InDNA,A,C,G,andTarelinkedby35esterbonds
betweendeoxyriboseandphosphate
 SecondaryStructure:DNADoubleHelix
InDNAtherearetwostrandsofnucleotidesthatwindtogether
inadoublehelix
thestrandsruninoppositedirections
thebasesarearearrangedinsteplikepairs
thebasepairsareheldtogetherbyhydrogenbonding
Thepairingofthebasesfromthetwostrandsisveryspecific
ThecomplimentarybasepairsareATandGC
twohydrogenbondsformbetweenAandT
threehydrogenbondsformbetweenGandC
Eachpairconsistsofapurineandapyrimidine,sotheyarethe
samewidth,keepingthetwostrandsatequaldistancesfrom
eachother
BasePairingintheDNADoubleHelix
 28.8:SecondaryStructureofDNA:TheDoubleHelix.
Initiallikewithlike,parallelhelix:
DoesnotfitwithwithChargaffsRule:A=T G=C
H
H N
N N dR
dR dR dR
N N N N O N
O N

O N H N N N
N
H
H H O O H H
H N N
H H H H
N
O N N H N
N
N O
N N N O
N N dR
dR dR dR
N N
N H
H

purine - purine pyrimidine - pyrimidine

Wrongtautomers!!

Watson,J.D.TheDoubleHelix,1968 16
Twopolynucleotidestrands,runninginoppositedirections
(antiparallel)andcoiledaroundeachotherinadoublehelix.
Thestrandsareheldtogetherbycomplementaryhydrogen
bondingbetweenspecificpairsofbases.
AntiparallelCGPair

Hydrogen Bond
O6 Hydrogen Bond
H
Donor N4
N H O N
Acceptor
Hydrogen Bond 5'
Acceptor
N3 N N1 Hydrogen Bond
N H N RO Donor
5' N N O
Hydrogen Bond RO
Acceptor O2 O O H N N2
Hydrogen Bond
Donor
H OR

OR
3'

3'

AntiparallelTAPair
H Hydrogen Bond
Hydrogen Bond
O4 O H N
N6 Donor
Acceptor N
5'
Hydrogen Bond
Donor
N3 N H N N RO N1 Hydrogen Bond
5' Acceptor
N N O
RO O O
OR
3'
OR 17
3'
DNAdoublehelix

major
groove
12
one
helical
turn
34 minor
groove
6

backbone:deoxyriboseandphosphodiesterlinkage
bases 18
28.9:TertiaryStructureofDNA:Supercoils.Eachcellcontains
abouttwometersofDNA.DNAispackagedbycoilingaround
acoreofproteinsknownashistones.TheDNAhistone
assemblyiscalledanucleosome.Histonesarerichislysine
andarginineresidues.

19
Pdbcode1kx5
 StorageofDNA
Ineukaryoticcells(animals,plants,fungi)DNAisstoredin
thenucleus,whichisseparatedfromtherestofthecellbya
semipermeablemembrane
TheDNAisonlyorganizedintochromosomesduringcell
replication
Betweenreplications,theDNAisstoredinacompactball
calledchromatin,andiswrappedaroundproteinscalled
histonestoformnucleosomes
 DNAReplication
Whenaeukaryoticcelldivides,theprocessiscalledmitosis
thecellsplitsintotwoidenticaldaughtercells
theDNAmustbereplicatedsothateachdaughtercellhasacopy
DNAreplicationinvolvesseveralprocesses:
first,theDNAmustbeunwound,separatingthetwostrands
thesinglestrandsthenactastemplatesforsynthesisofthenew
strands,whicharecomplimentaryinsequence
basesareaddedoneatatimeuntiltwonewDNAstrandsthat
exactlyduplicatetheoriginalDNAareproduced
Theprocessiscalledsemiconservativereplicationbecauseone
strandofeachdaughterDNAcomesfromtheparentDNAandone
strandisnew
Theenergyforthesynthesiscomesfromhydrolysisofphosphate
groupsasthephosphodiesterbondsformbetweenthebases
SemiConservativeDNAReplication
 DirectionofReplication
TheenzymehelicaseunwindsseveralsectionsofparentDNA
AteachopenDNAsection,calledareplicationfork,DNA
polymerasecatalyzestheformationof53esterbondsofthe
leadingstrand
Thelaggingstrand,whichgrowsinthe35direction,is
synthesizedinshortsectionscalledOkazakifragments
TheOkazakifragmentsarejoinedbyDNAligasetogivea
single35DNAstrand
EnzymesandProteinsInvolvedinDNAReplication
 RibonucleicAcid(RNA)
RNAismuchmoreabundantthanDNA
ThereareseveralimportantdifferencesbetweenRNAandDNA:
thepentosesugarinRNAisribose,inDNAitsdeoxyribose
inRNA,uracilreplacesthebasethymine(UpairswithA)
RNAissinglestrandedwhileDNAisdoublestranded
RNAmoleculesaremuchsmallerthanDNAmolecules
TherearethreemaintypesofRNA:
ribosomal(rRNA),messenger(mRNA)andtransfer(tRNA)
TypesofRNA
 RibosomalRNAandMessengerRNA
Ribosomesarethesitesofproteinsynthesis
theyconsistofribosomalDNA(65%)andproteins(35%)
theyhavetwosubunits,alargeoneandasmallone
MessengerRNAcarriesthegeneticcodetotheribosomes
theyarestrandsofRNAthatarecomplementarytothe
DNAofthegenefortheproteintobesynthesized
 TransferRNA
TransferRNAtranslatesthegeneticcodefromthemessengerRNA
andbringsspecificaminoacidstotheribosomeforproteinsynthesis
EachaminoacidisrecognizedbyoneormorespecifictRNA
tRNAhasatertiarystructurethatisLshaped
oneendattachestotheaminoacidandtheotherbindstothemRNA
bya3basecomplimentarysequence
 ProteinSynthesis
Thetwomainprocessesinvolvedinproteinsynthesisare
theformationofmRNAfromDNA(transcription)
theconversionbytRNAtoproteinattheribosome(translation)
Transcriptiontakesplaceinthenucleus,whiletranslationtakes
placeinthecytoplasm
GeneticinformationistranscribedtoformmRNAmuchthesame
wayitisreplicatedduringcelldivision
 Transcription
Severalstepsoccurduringtranscription:
asectionofDNAcontainingthegeneunwinds
onestrandofDNAiscopiedstartingattheinitiationpoint,
whichhasthesequenceTATAAA
anmRNAissynthesizedusingcomplementarybasepairing
withuracil(U)replacingthymine(T)
thenewlyformedmRNAmovesoutofthenucleusto
ribosomesinthecytoplasmandtheDNArewinds
 RNAPolymerase
Duringtranscription,RNApolymerasemovesalongtheDNA
templateinthe35directiontosynthesizethecorresponding
mRNA
ThemRNAisreleasedattheterminationpoint
 ProcessingofmRNA
GenesintheDNAofeukaryotescontainexonsthatcode
forproteinsalongwithintronsthatdonot
BecausetheinitialmRNA,calledapreRNA,includesthe
noncodingintrons,itmustbeprocessedbeforeitcanbe
readbythetRNA
WhilethemRNAisstillinthenucleus,theintronsare
removedfromthepreRNA
TheexonsthatremainarejoinedtoformthemRNAthat
leavesthenucleuswiththeinformationforthesynthesisof
protein
RemovingIntronsfrommRNA
 RegulationofTranscription
AspecificmRNAissynthesizedwhenthecellrequiresa
particularprotein
Thesynthesisisregulatedatthetranscriptionlevel:
feedbackcontrol,wheretheendproductsspeedupor
slowthesynthesisofmRNA
enzymeinduction,whereahighlevelofareactantinduces
thetranscriptionprocesstoprovidethenecessaryenzymes
forthatreactant
Regulationoftranscriptionineukaryotesiscomplicatedand
wewillnotstudyithere
 RegulationofProkaryoticTranscription
Inprokaryotes(bacteriaandarchebacteria),transcriptionof
proteinsisregulatedbyanoperon,whichisaDNAsequence
precedingthegenesequence
Thelactoseoperonconsistsofacontrolsiteandthegenes
thatproducemRNAforlactoseenzymes
 LactoseOperonandRepressor
Whenthereisnolactoseinthecell,aregulatorygene
producesarepressorproteinthatpreventsthesynthesis
oflactoseenzymes
therepressorturnsoffmRNAsynthesis
 LactoseOperonandInducer
Whenlactoseispresentinthecell,somelactosecombineswith
therepressor,whichremovestherepressorfromthecontrolsite
Withouttherepressor,RNApolymerasecatalyzesthesynthesis
oftheenzymesbythegenesintheoperon
Theleveloflactoseinthecellinducesthesynthesisofthe
enzymesrequiredforitsmetabolism
RNA Polymerase
 TheGeneticCode
Thegeneticcodeisfoundinthesequenceofnucleotidesin
mRNAthatistranslatedfromtheDNA
AcodonisatripletofbasesalongthemRNAthatcodesfora
particularaminoacid
Eachofthe20aminoacidsneededtobuildaproteinhasatleast2
codons
Therearealsocodonsthatsignalthestartandendofa
polypeptidechain
Theaminoacidsequenceofaproteincanbedeterminedby
readingthetripletsintheDNAsequencethatarecomplementary
tothecodonsofthemRNA,ordirectlyfromthemRNAsequence
TheentireDNAsequenceofseveralorganisms,including
humans,havebeendetermined,however,
onlyprimarystructurecanbedeterminedthisway
doesntgivetertiarystructureorproteinfunction
mRNACodonsandAssociatedAminoAcids
 ReadingtheGeneticCode
Supposewewanttodeterminetheaminoacidscodedfor
inthefollowingsectionofamRNA

5CCUAGCGGACUU3

Accordingtothegeneticcode,theaminoacidsforthese
codonsare:

CCU=Proline AGC=Serine
GGA=Glycine CUU=Leucine

ThemRNAsectioncodesfortheaminoacidsequenceof
ProSerGlyLeu
 TranslationandtRNAActivation

OncetheDNAhasbeen
transcribedtomRNA,the
codonsmustbetranlatedtothe
aminoacidsequenceofthe
protein
Thefirststepintranslationis
activationofthetRNA
EachtRNAhasatripletcalled
ananticodonthatcomplements
acodononmRNA
AsynthetaseusesATP
hydrolysistoattachanamino
acidtoaspecifictRNA
 InitiationandTranslocation
InitiationofproteinsynthesisoccurswhenamRNAattachesto
aribosome
OnthemRNA,thestartcodon(AUG)bindstoatRNAwith
methionine
ThesecondcodonattachestoatRNAwiththenextaminoacid
Apeptidebondformsbetweentheadjacentaminoacidsatthe
firstandsecondcodons
ThefirsttRNAdetachesfromtheribosomeandtheribosome
shiftstotheadjacentcodononthemRNA(thisprocessiscalled
translocation)
Athirdcodoncannowattachwherethesecondonewasbefore
translocation
 Termination
Afterapolypeptidewithalltheaminoacidsforaproteinis
synthesized,theribosomereachesthethestopcodon:
UGA,UAA,orUAG
ThereisnotRNAwithananticodonforthestopcodons
Therefore,proteinsynthesisends(termination)
Thepolypeptideisreleasedfromtheribosomeandthe
proteincantakeonits3Dstructure
(someproteinsbeginfoldingwhilestillbeingsynthesized,
whileothersdonotfoldupuntilafterbeingreleasedfrom
theribosome)