Nucleic acids

21 - 1©Chemistry for Allied Health: Chap 22 - DNA

Nucleosides & Nucleotides

Nucleic Acids

DNA & Replication

RNA & Transcription

Genetic Code & Protein Synthesis

Genetic Mutations

Recombinant DNA

Viruses

Nucleic acidsNucleic acids


Nucleic acidsNucleic acids

Nucleic acidsNucleic acids: – Maintain genetic informationMaintain genetic information– Determine Protein SynthesisDetermine Protein Synthesis

DNADNA = deoxydeoxyribonucleic acid– “Master Copy” for most cell information.– Template for RNA

RNA =RNA = ribonucleic acid– Transfers information from DNA– Template for Proteins


Nucleic AcidsNucleic AcidsIn chromosomes

(in nucleus)

Have genesgenes

1 gene

1 enzyme

EnzymesEnzymes determine determine

external & internal characteristicsexternal & internal characteristics


NUCLEIC ACIDSNUCLEIC ACIDS

Long chains (polymers) of repeating nucleotides.nucleotides.– Each nucleotide has 3 parts:3 parts:

A A phosphate unitphosphate unit H H

OO

H

H

OH

H

H

HO

A sugarsugar

A heterocyclic heterocyclic Amine BaseAmine BaseN

H

P OH

O

OH

HO


NucleoNucleottide ide = phosphate + sugar + base= phosphate + sugar + baseNucleoNucleottide ide = phosphate + sugar + base= phosphate + sugar + base

P

O

O

ON

H H

OH

OH

H

H

O

-N-glycosidiclinkage

-N-glycosidiclinkage

BaseBase

SugarSugar

PhosphatePhosphate

Nucleoside = Nucleoside = sugar + basesugar + baseNucleoside = Nucleoside = sugar + basesugar + base


Nucleic AcidsNucleic Acids

Nucleic AcidsNucleic Acids = polymerspolymers of Nucleotides.Nucleotides.

phosphate sugar

base

SS SS SSSSSSSS

BB BB BBBBBBBB

PPPP PP PPPPPP


THE SUGAR PARTTHE SUGAR PART• The major difference between RNA and DNA is

the different form of sugar used.

OHOCH2

H HHH

OH OHOH

OHOHOCH2

H HHH

OH HH

OH

Ribose C5H10O5

in RNADeoxyDeoxyRibose C5H10O4

in DNA

The difference is at carbon #2carbon #2.


The Nitrogenous BasesThe Nitrogenous Bases

5 bases5 bases used fall in two classestwo classes

Purines Purines & & PyrimidinesPyrimidines

N

N

N

NH

A double ringdouble ring (6 & 5 members)

A single ringsingle ring(6 membered)

N

N


Pyrimidines:Pyrimidines:

The Nitrogenous BasesThe Nitrogenous Bases

Purines:Purines:N

N

N

N

NH2

H

N

N

N

NH

H2N

O

H

N

N

O

O

CH3

H

HN

N

O

O

H

H N

NO

H

H

NH2

Adenine (A)Adenine (A)Adenine (A)Adenine (A) Guanine (G)Guanine (G)Guanine (G)Guanine (G)

Thiamine (T)Thiamine (T)In In DNADNA only onlyThiamine (T)Thiamine (T)In In DNADNA only only

Uracil (U)Uracil (U)In In RNARNA only only

Uracil (U)Uracil (U)In In RNARNA only only

Cytosine (C)Cytosine (C)Cytosine (C)Cytosine (C)


NucleotidesNucleotides

deoxyadenosine 5’ monophosphate(dAMP)

deoxyadenosine 5’ monophosphate(dAMP)

Name based on sugar & base names

followed by the #of phosphates..

N

N

N

N

NH2

P

O

O

O

H H

OH

OH

H

H

O

1'

2'3'

4'

5'


Primary structurePrimary structure

Phosphate bondsPhosphate bondslink DNA or RNAlink DNA or RNAnucleotides togethernucleotides togetherin a linear sequence.

O|

O -- P -- O --||O

-CH2 O

OH

O|

O -- P -- O --||O

-CH2 O

O|

O -- P -- O --||O

-CH2 O

O|

O -- P -- O --||O

-CH2 O

NC

C

CCN

N

N

CH

NH2

|

H

NC

C

CCNO

NH2

|

H

H

NC

C

CCN

N

N

CH

O||

H

H2N

NC

C

CCNO

H

H

O|| CH3

Similar to proteinswith their peptidebonds and sidegroups.


DNA - Primary StructureDNA - Primary Structure


Base pairing and H-bondingBase pairing and H-bonding

N

N

O| |

- H

N - H

N

NN

N

O| |

H - N

N

N O| |

O| |

H3C

- H

guanine cytosine

thymine adenineN

N N

N|

HH

N

H- bonding between purines and pyrimidinespurines and pyrimidines..


DNA - DNA - Secondary StructureSecondary Structure

Complementary Base PairingGuanine pairs with CytosinePosition of H bonds and distance match



Complementary Base PairingAdenine pairs with ThyminePosition of H bonds and distance match


Hydrogen bondingHydrogen bonding

Each base wants toform either two or three hydrogen bonds.

That’s why only certain bases will form pairs.

G

T

C

A

C G

A

C

T

G


Sugar-Sugar-phosphate phosphate backbonebackboneDNA coilscoils around outsideoutside of of attached attached basesbases like a spiral stair case.

Results in a double helix structure.


The double helixThe double helix

The combination of the stairstep sugar-phosphate backbone and the bonding between pairs resultsin a double helix.

The combination of the stairstep sugar-phosphate backbone and the bonding between pairs resultsin a double helix.

Distance betweenbases = 0.34 nm

2 nmbetweenstrands

One complete

twist is 3.4 nm



Complementary Base Pairing


• The actual chain is like a coiled spring.– It is something similar to what happens when

protein chains form an alpha helix.• It is the sequence (order) of the amines coming

off of the backbone that give us all our genetic information– Just like the sequence of words in a sentence

give it meaning.– Of the like in words meaning just sentence a

give sequence it. (Get my meaning ? )


• Crick and Watson (1962 Nobel Prize)

– Proposed the basic structure of DNA

– 2 strands wrap around each other

– Strands are connected by H-bonds between the amines.• Like steps of a spiral

staircase


ChromosomesChromosomes

Chromosomes consists of DNA strands coiledaround protein - histomes. The acidic DNA’s areattracted to the basic histones.



ChromosomesChromosomes

The normal number of chromosome pairs varies among the species.

AnimalAnimal Pairs Pairs PlantPlant PairsPairsMan 23 Onion 8Cat 30 Rice 14Mouse 20 Rye 7Rabbit 22 Tomato 12Honeybee, White pine 12

male 8 Adder’s 1262female 16 tounge fern


DNA: Self - ReplicationDNA: Self - Replication

• When a cell nucleus divides, the bridging hydrogen bonds break (with the aid of aid of enzymesenzymes) and the intertwined strands unwind from each other.

• The amines left stickingamines left sticking out from each strand are now free to pick up new partnersfree to pick up new partners from the plentiful supply present in the cell.

PS

PS

PS

PS

A T G C

amine bases hanging off the nucleotide chain.


PS

PS

PS

PS

A T G C

P S

T

P S

G

Each A picks up a T, each C picks up a G, etc...

Eventually, every amine group is reunited withits complimentary amine and the lost partner strandis reformed.They now twine around each other to form thenew Double helix.


DNA DNA ReplicationReplication


Replication of DNAReplication of DNA

ReplicationReplication occurs on both halvesboth halvesin opposite directions.opposite directions.





Okazaki fragments



Okazaki fragments


• It is the linear sequence of paired baseslinear sequence of paired bases (amines) along the DNA molecule that constitutes the Genetic CodeGenetic Code.

– Each seriesseries of amines that codes forcodes for a particular proteinprotein is called a GeneGene.


Flow of genetic informationFlow of genetic information

Replication

DNADNA

RNARNA

ProteinProtein

Transcription

Translation

Flow of information

isone way

only.


RNARNASingle strands of nucleotidesSingle strands of nucleotides where riboseribose is used in the sugar-phosphate backbone.

Several secondary structures (typesSeveral secondary structures (types) based on the particular role it plays.

RNA RNA is produced by transcription of genesproduced by transcription of genes along a strand of DNA.

DNADNA may contain all the informationall the information but RNA RNA does all of the workdoes all of the work. (Kinda like the architect and the engineer. Or better yet, the teacher and the student. )


Classes of RNAClasses of RNA

Messenger RNA - mRNAMessenger RNA - mRNAIt carries a copy of the genetic information contained in DNA. Used as pattern to make proteins.


RNA - THE MESSENGER (m/RNA)RNA - THE MESSENGER (m/RNA)

• DNADNA in the nucleus in the nucleus of the cell directs the directs the sythesissythesis of an RNARNA molecule molecule.– The RNARNA will carry the sequence of amines

found on a particular portion of the DNA• Only a portion of a Only a portion of a DNADNA strand is used to make

any given RNARNA.. • There needs to be a way to start and stopstart and stop

transcription.• The DNADNA has systems of promoter promoter and and

terminationtermination base sequences.


RNA synthesisRNA synthesis

In the first step, RNA polymeraseRNA polymerase bindsto a promotorpromotor sequenceon the DNA chain.

This insuresinsures that transcription occurs in the correct directioncorrect direction.

The initial reaction is toseparate the twoseparate the twoDNA strandsDNA strands.



initiationsequence

terminationsequence

‘Special’ baseSpecial’ basesequencessequences in theDNA indicatewhere RNARNAsynthesis startssynthesis startsand stops.and stops.



Once the terminationsequence isreached, thenew RNA moleculenew RNA moleculeand the RNA synthaseare released.released.

The DNA recoils.The DNA recoils.


• The messenger RNAmessenger RNA (mRNA) move outside the nucleus to the cytoplasmto the cytoplasm where RibosomesRibosomes are anxiously awaiting their arrival.

rRNA40 S

60 SrRNA



rRNA40 S

60 SrRNA



rRNA40 S

60 SrRNA



rRNA40 S

60 SrRNA


rRNA40 S

60 SrRNA

Ribosomal RNA – rRNARibosomal RNA – rRNA: Platform for protein synthesis. Holds mRNA in place and helps assemble proteins.


40 S

AUG GCU AUG UUG

5’

3’

rRNArRNA

60 S

•The RibosomesRibosomes are like train stationslike train stations

–The mRNA is the trainmRNA is the train slowly moving through the station.

rRNArRNA

Codons

mRNAmRNA


Transfer RNA Transfer RNA - tRNA- tRNA =• relatively small small compared to other RNA’s

(70-90 bases.)70-90 bases.)• transports amino acidstransports amino acids to site of protein synthesis.

A

C

C

A

C

C

U

C

G

U

CU

U

C

G

G

G

G

G

CC GGG

CC GG

A CGG

CC GGU

C

C

C

C

U

C

A

U

G

G

A

G

G

G

G

GU

U

CC G

U

C GC

AU

G

G

C

U

AG U

A GU

G

GC

HO-A

C

C

A

C

C

U

C

G

U

CU

U

C

G

G

G

G

G

CC GGG

CC GG

A CGG

CC GGU

C

C

C

C

U

C

A

U

G

G

A

G

G

G

G

GU

U

CC G

U

C GC

AU

G

G

C

U

AG U

A GU

G

GC

HO-


Anticodons on t-RNAAnticodons on t-RNA

A

C

C

A

C

C

U

C

G

U

CU

U

C

G

G

G

G

G

CC GGG

CC GG

A CGG

CC GGU

C

C

C

C

U

C

A

U

G

G

A

G

G

G

G

GU

U

CC G

U

C GC

AU

G

G

C

U

AG U

A GU

G

GC

HO-

Site of aminoacid attachment

Site of aminoacid attachment

Three base anticodon site

Three base anticodon site

Point ofattachmentto mRNA

Point ofattachmentto mRNA


Amino acid codonsAmino acid codons

alanine GCA, GCC, GCGGCU, AGA, AGG

arginine AGA, AGG, CGACGC, CGG, CGU

asparagine AAC, AAUaspartate GAC, GAU cysteine UGC, UGUglutamate GAA, GAGglutamine CAA, CAGglycine GAA, GCC, GGG

GGUhistidine CAC, CAUisoleucine AUA, AUC, AUUleucine CUA, CUC, CUG

CUU, UUA, UUG

lysine AAA, AAGmethionine AUGphenylalanine UUC, UUUproline CCA, CCC

CCG, CCUserine UCA, UCC

UCG, UCU AGC, AGU

threonine ACA, ACC ACG, ACU

tryptophan UGGtyrosine UCA, UCUvaline GUA, GUC

GUG, GUU


Protein SynthesisProtein Synthesis1: Activation1: Activation

Each AA is activated by reacting with an ATP

The activated AA is then attached to particular tRNAtRNA... (with the correct anticodon)

C G A

fMET

anticodon

activated AA


adenosine 5’ triphosphate(ATP)

adenosine 5’ triphosphate(ATP)

N

N

N

N

NH2

P

O

O

O

H H

OH

OH

H

H

O

1'

2'3'

4'

5'

Aa +


TranslationTranslation

40S

AUG GCU AUG UUG mRNA

5’

3’

Initiationfactors

ribosome unit

PPsitesite AA site site



40S


5’

3’

Initiationfactors

ribosome unit

U A C

fMET



U A C

fMET


40S ribosome unit


5’

3’

60S



U A C

fMET


40S ribosome unit


5’

3’

60S


C G A

Ala


ribosome unit


5’

3’


U A C

fMET

C G A

Ala

peptide bondforms


ribosome unit


5’

3’


U A C

fMET

C G A

Ala

peptide bondforms


ribosome unit

GCU UUC UUGmRNA

5’

3’


C G A

Ala

peptide bond

Met

Z Z Z

Amino Acid


ribosome unit

GCU UUC UUGmRNA

5’

3’


C G A

Ala

peptide bondforms

Met

? ? ?

???


TerminationTermination

After the last translocation (the last codon is a STOP), no more AA are added.

“Releasing factors” cleave the last AA from the tRNA

The polypeptide is complete


CodonsCodons

There are two additional types of codons:

Initiation Initiation AUGAUG(same as methionine)

TerminationTermination UAG, UAA, UGAUAG, UAA, UGA

A total of 64 condons are used for all aminoacids and for starting and stopping. All proteinsynthesis starts with methionine. After the poly-peptide has been made, an enzyme removes thisamino acid.


Amino acid codonsAmino acid codons

alanine GCA, GCC, GCGGCU, AGA, AGG

arginine AGA, AGG, CGACGC, CGG, CGU

asparagine AAC, AAUaspartate GAC, GAU cysteine UGC, UGUglutamate GAA, GAGglutamine CAA, CAGglycine GAA, GCC, GGG

GGUhistidine CAC, CAUisoleucine AUA, AUC, AUUleucine CUA, CUC, CUG

CUU, UUA, UUG

lysine AAA, AAGmethionine AUGphenylalanine UUC, UUUproline CCA, CCC

CCG, CCUserine UCA, UCC

UCG, UCU AGC, AGU

threonine ACA, ACC ACG, ACU

tryptophan UGGtyrosine UCA, UCUvaline GUA, GUC

GUG, GUU


Recombinant DNARecombinant DNA

Circular DNA found in bacteriaE.Coli plasmid bodiesRestriction endonucleases cleave DNA at

specific genesResult is a “sticky end”Addition of a gene from a second

organismSpliced DNA is replaced and organism

synthesizes the new protein


Recombinant DNARecombinant DNA

Bacterium

Remove gene segment

DNAPlasmid sticky ends

Cut genefor insulin

Replace inbacterium

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