Chapter 9, Molecular Structure of DNA and RNA

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    LECTURE 1

    Introduction to

    DNA and RNA(Chapter 09)

    Slides 1!"# $"% "%"'

    On your own:Slides !$%# %9"$# "&!

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    INTR6DUCTI6N

    7 -enetics8 Stud o5 the structure 5unction

    transission o5 *enes

    7 6nl living organismshae *enes

    7 To understand *enetics .e .ill start .ith the

    4uestion8 :;hat is Li5e Characteristics shared ? all liin* 5ors ?ut not ?

    nonliin* 5ors

    2

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    ;hat is the role o5 DNA in li5e :Duh@a (A .heel out o5 @ilter)

    > I /ad Trou?le in -ettin* to Solla Solle. (.here there arent anpro?les at least er 5e.)

    LIFE (GENES)

    (negative entropy)

    UNIVERSE

    (entropy)

    3

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    /o. does li5e 5i*ht entrop In5oration and ne*atie entrop

    >Analo* s di*ital

    7 Di55erent or*aniss hae di55erent *enes#

    di55erent strate*ies 5or the surial o5 the *enes

    and their transission to the net *eneration

    7 Those *enes that ?uilt the ?est :surial

    achines= are still .ith us toda7 The ast aGorit o5 *enes .ere lost

    7 This is a ?lind undirected process

    6

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    ,6LECULAR -ENETICS

    7 Chapter 9 eaines the *enetic aterial in detail8olecular *enetics> The stud o5 DNA structure and 5unction at the

    olecular leel

    7 Recent draatic adances in techni4ues andapproaches hae *reatl epanded ourunderstandin* o5 olecular *enetics>And also o5 transission and population *enetics

    7 To a lar*e etent our @no.led*e o5 *eneticscoes 5ro our @no.led*e o5 the olecularstructure o5 DNA and RNA

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    921 IDENTIBICATI6N 6B DNA AS

    T/E -ENETIC ,ATERIAL

    7 To 5ul5ill its role the *enetic aterial ust eet

    seeral criteria

    > 12 In5oration8 It ust contain the in5oration necessarto a@e an entire or*anis

    > !2 Transission8 It ust ?e passed 5ro parent to

    o55sprin*

    > $2 Replication8 It ust ?e copied7 In order to ?e passed 5ro parent to o55sprin*

    > %2 Hariation8 It ust ?e capa?le o5 chan*es

    7 To account 5or the @no.n phenotpic ariation in each species

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    921 IDENTIBICATI6N 6B DNA AS

    T/E -ENETIC ,ATERIAL

    7 The data o5 an *eneticists includin*

    ,endel .ere consistent .ith these 5our

    properties> /o.eer the cheical nature o5 the *enetic aterialcannot ?e identi5ied solel ? *enetic crosses

    7 Indeed the identi5ication o5 DNA as the *enetic

    aterial inoled a series o5 outstandin*eperiental approaches

    > These .ill ?e eained net

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    Brederic@ -ri55ith Eperients .ith

    Streptococcus pneumoniae

    7 -ri55ith studied a ?acteriu (pneumococci) [email protected] as Streptococcus pneumoniae

    7 S. pneumoniaecoes in t.o strains

    > SSooth7 Secrete a polsaccharide capsule

    > 3rotects ?acteriu 5ro the iune sste o5 anials

    7 3roduce sooth colonies on solid edia

    > RRou*h7 Una?le to secrete a capsule

    7 3roduce colonies .ith a rou*h appearance

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    In 19!& -ri55ith conducted eperients usin* t.o

    strains o5 S. pneumoniae8 tpe IIIS and tpe IIR

    12 InGect ouse .ith lie tpe IIIS ?acteria ,ouse died

    Tpe IIIS ?acteria recoered 5ro the ouses ?lood

    !2 InGect ouse .ith lie tpe IIR ?acteria

    ,ouse suried No liin* ?acteria isolated 5ro the ouses ?lood

    $2 InGect ouse .ith heat@illed tpe IIIS ?acteria ,ouse suried

    No liin* ?acteria isolated 5ro the ouses ?lood

    %2 InGect ouse .ith lie tpe IIR heat@illed tpe IIIS cells ,ouse died

    Tpe IIIS ?acteria recoered 5ro the ouses ?lood

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    !igure ".#

    Living type S bacteria wereinjected into a mouse.

    Mouse died

    Deadtype S

    Livetype R

    Mouse died Mouse survived Mouse survived

    Living type R bacteria wereinjected into a mouse.

    Heat-killed type S bacteriawere injected into a mouse.

    Living type R and heat-killedtype S bacteria were injectedinto a mouse.

    Type S bacteria were isolatedfrom the dead mouse.

    No living bacteria were isolatedfrom the mouse.

    No living bacteria were isolatedfrom the mouse.

    Type S bacteria were isolatedfrom the dead mouse.

    (a) Live type S (b) Live type R (c) Dead type S (d) Live type R + dead type S

    Afterseveraldays

    Afterseveraldays

    Afterseveraldays

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    Afterseveraldays

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    -ri55ith concluded that soethin* 5ro the dead

    tpe IIIS ?acteria .as trans5orin* tpe IIR

    ?acteria into tpe IIIS /e called this process trans5oration

    The su?stance that allo.ed this to happen .astered thetrans5oration principle -ri55ith did not @no. .hat it .as

    Su**ested that the *enetic in5oration olecule is

    resistant to hi*h teperature ,ost proteins de*rade at hi*h teperature

    Connect -ri55iths eperient to Eperient 1 (la?)

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    ;e no. @no. that the 5oration o5 the capsule is

    *uided ? the ?acterias *enetic aterial

    Trans5ored R ?acteria acquireda *ene 5ro the deadlsed S ?acterua that directs the cell ho. to a@e a

    capsule polsachharide

    Variationeists in a?ilit to a@e capsule (R cells carr a

    non5unction allele 5or the *ene) The *ene re4uired to create a capsule is replicatedand

    transmitted5ro other to dau*hter cells

    6nce R cells ac4uired it the passed the trait to their

    :o55sprin*= The olecular nature o5 the trans5orin* principle

    .as deterined usin* eperiental approaches

    that incorporated arious ?iocheical techni4ues14

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    The Eperients o5

    Aer ,acLeod and ,cCart

    7 Aer ,acLeod and ,cCart realied that -ri55ithso?serations could ?e used to identi5 the *enetic aterial

    7 The carried out their eperients in the 19%0s

    > At that tie it .as @no.n that DNA RNA proteins andcar?ohdrates are the aGor constituents o5 liin* cells

    7 The prepared cell etracts 5ro tpe IIIS cells and puri5iedeach tpe o5 acroolecule> 6nl the etract that contained puri5ied DNA .as a?le to conert

    tpe IIR ?acteria into tpe IIIS

    > Treatent o5 the DNA etract .ith RNase or protease did noteliinate trans5oration

    > Treatent .ith DNase did

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    !igure ".$

    Aer et al.conducted the 5ollo.in* eperients To 5urther eri5 that DNA and not a containant (RNA

    or protein) is the *enetic aterial

    Mix Mix Mix Mix

    Type R

    cells

    Type R

    cells

    Type S

    DNAextract

    Type R

    cells

    Type S

    DNAextract+

    DNase

    Type R

    cells

    Type S

    DNAextract+

    RNase

    Type R

    cells

    Type S

    DNAextract+

    protease

    Transformed Transformed Transformed

    1 2 3 4 5

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    Allow sufficient time for the DNA to be taken up by the type R bacteria. Only a small percentage of the type R bacteria will be transformed to type S.

    Add an antibody that aggregates type R bacteria (that have not been transformed). The aggregated bacteria are removed by gentle centrifugation.

    Plate the remaining bacteria on petri plates. Incubate overnight.

    16

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    Head

    Tail fiber

    Base plate

    Sheath

    DNA(inside thecapsid head)

    Eperient 9A /ershe and Chase

    Eperient .ith Jacteriopha*e T!7 In 19"! Al5red /ershe and ,arsha Chase

    proided 5urther eidence that DNA is the *enetic

    aterial

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    The studied the

    ?acteriopha*e T!

    It is relatiel siplesince its coposed o5

    onl t.o

    acroolecules DNA and protein

    !igure ".%

    ,ade upo5 protein

    Inside the

    capsid

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    !igure ".&

    Life cycle of

    bacteriophage T2

    Phage binds to host cell.

    Capsid

    Bacterialchromosome

    Bacterialcell wall

    Phage injects itsDNA into host cell.

    The expression ofphage genes leadsto the synthesis of

    phage components.

    Phage componentsare assembled.

    Host cell lysesand new phagesare released.

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    Genetic material

    3ha*e coat (protein)

    precariousl attached

    to ?acterial cell

    DNA inside o5 cell

    18

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    7 The /ershe and Chase eperient can ?e

    suaried as 5ollo.s8

    > Used radioisotopes to distin*uish DNA 5ro proteins

    7 $!3 la?els DNA speci5icall

    7 $"S la?els protein speci5icall

    > Radioactiella?eled pha*es .ere used to in5ect

    nonradioactie Escherichia colicells

    >A5ter allo.in* su55icient tie 5or in5ection to proceed

    the residual pha*e particles .ere sheared o55 the cells

    7 K 3ha*e *hosts and E. colicells .ere separated

    > Radioactiit .as onitored usin* a scintillation

    counter

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    The /pothesis

    > 6nl the *enetic aterial o5 the pha*e is inGectedinto the ?acteriu

    7 Isotope la?elin* .ill reeal i5 it is DNA or protein

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    Testin* the /pothesis

    Re5er to Bi*ure 92"

    20

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    !igure ".' Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display

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    E$perimental level %on&ept"al level

    Grow bacterial cells. Divide intotwo fasks.

    1.

    Into one fask add 35!"labeled #$a%e& int$e second fask add 32'"labeled #$a%e.

    2.

    (llow in)ection to occ*r.3.

    (%itate sol*tions in blenders )ordi+erent len%t$s o) ti,e to s$ear t$ee,#t- #$a%es o+ t$e bacterial cells.

    4.

    entri)*%e at 10000 r#,.5.

    /$e $eav- bacterial cells sedi,ent to t$e

    #ellet w$ile t$e li%$ter #$a%es re,ain int$e s*#ernatant. !ee (##endi )ore#lanation o) centri)*%ation.

    6.

    o*nt t$e a,o*nt o) radioisoto#e int$e s*#ernatant wit$ a Gei%er co*nter.o,#are it wit$ t$e startin% a,o*nt.

    7.

    !*s#ension o)E. coli cells

    32'"labeled/2 #$a%e

    35!"labeled/2 #$a%e

    !*#ernatantwit$35!"labelede,#t- #$a%e

    'ellet wit$*nlabeledD( inin)ectedE. coli cells

    !*#ernatantwit$*nlabelede,#t- #$a%e

    'ellet wit$32'"labeledD( inin)ectedE. coli cells

    !*s#ension o)E. coli in)ected wit$35!"labeled #$a%e

    !*s#ension o)E. coli in)ected wit$32'"labeled #$a%e

    35!"labeled#rotein ca#sid

    acterial cell

    ()ter blendin%

    iral %enetic,aterial

    iral%enetic,ateriallabeled

    acterialcell

    !$eared e,#t-#$a%es labeled

    !$eared e,#t-#$a%e labeled

    32'"labeledD(

    !$earede,#t-#$a%es*nlabeled

    !$earede,#t-

    #$a%e

    21

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    The Data

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    80%Blending removes 80%of35S fromE. colicells.

    35%Most of the32P (65%)remains with intactE. colicells.

    Totalisotopei

    nsupernatant(%)

    Agitation time in blender (min)

    100

    80

    60

    40

    20

    00 1 2 3 4 5 6 7 8

    Data from A. D. Hershey and Martha Chase (1952) Independent Functions of Viral Protein and Nucleic Acid in Growth ofBacteriophage.Journal of General Physiology36, 3956.

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    Extracellular35S

    Extracellular32P

    22

    I i h D

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    80%Blending removes 80%of35S fromE. colicells.

    35%

    Most of the32

    P (65%)remains with intactE. colicells.

    Totaliso

    topeinsupernatant(%)

    Agitation time in blender (min)

    100

    80

    60

    40

    20

    00 1 2 3 4 5 6 7 8

    Data from A. D. Hershey and Martha Chase (1952) Independent Functions of Viral Protein and Nucleic Acid in Growth ofBacteriophage.Journal of General Physiology36, 3956.

    Extracellular35S

    Extracellular32P

    Interpretin* the Data

    9-18

    ,ost o5 the $"S .as 5ound

    in the supernatantJut onl a sall

    percenta*e o5 $!3

    These results su**est that DNA is inGected into the ?acterial ctoplasdurin* in5ection

    Data is not conclusie since less than 100 o5 the DNA or protein

    ended up in the cell or supernatant

    Data is consistent .ith the hpothesis that DNA is the *enetic

    aterial 23

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    In 19" A2 -ierer and -2 Schra isolated RNA

    5ro the to?acco osaic irus (T,H) a plant irus 3uri5ied RNA caused the sae lesions as intact T,H

    iruses There5ore the iral *enoe is coposed o5 RNA

    Since that tie an RNA iruses hae ?een

    5ound Re5er to Ta?le 921

    RNA Bunctions as the -enetic ,aterial

    in Soe Hiruses

    24

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    25

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    92! NUCLEIC ACID

    STRUCTURE > On Your Own7 DNA and RNA are lar*e acroolecules .ith

    seeral leels o5 copleit

    > 12 Nucleotides 5or the repeatin* unit o5 nucleic acids> !2 Nucleotides are lin@ed to 5or a linear strando5

    RNA or DNA

    > $2 T.o strands can interact to 5or a dou?le heli

    > %2 The $D structure o5 DNA results 5ro 5oldin* and?endin* o5 the dou?le heli2 Interaction o5 DNA .ith

    proteins produces chroosoes .ithin liin* cells

    > Re5er to 5i*2 92

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    !igure ".(

    CC

    G

    AA

    GA

    T

    GG

    TT TA

    A

    G

    C

    A

    T

    ATT TAG

    C

    Nucleotides

    Single strand

    Double helix

    Three-dimensional structure

    ATCGCA A

    TCATGC

    AATCGCA

    GCA T

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    The nucleotideis the repeatin* structural unit o5DNA and RNA

    It has three coponents A phosphate *roup

    A pentose su*ar

    A nitro*enous ?ase

    Re5er to Bi*ure 92'

    Nucleotides

    28

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    9-24!igure ".)

    Phosphate group Sugars

    D-Deoxyribose (in DNA)

    Purines(double ring)

    Pyrimidines(single ring)

    Bases

    OO

    O

    O

    P

    H

    H

    H

    HO

    OHOHOCH2

    HH

    D-Ribose (in RNA)

    H

    OH

    H

    HO

    OHOHOCH2

    HH

    Uracil (U) (in RNA)Thymine (T) (in DNA)

    Cytosine (C)

    Adenine (A)

    Guanine (G)

    NH2

    N

    HH

    H

    H

    H

    O

    N

    43

    2

    156

    7

    8

    9

    43

    21

    5

    6

    O

    CH3 H

    432

    156

    7

    8

    9

    5M

    O

    NH2

    H

    HN

    N

    N

    N

    NH2

    N

    N

    H

    N

    N

    NH

    H O

    N43

    21

    5

    6

    O

    HH O

    43

    21

    5

    6

    N

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    4M 1M

    2M3M

    5M

    4M 1M

    3M 2M

    N

    29

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    HH

    H

    OCH2

    Base

    (a) Repeating unit of deoxyribonucleic acid (DNA)

    (b) Repeating unit of ribonucleic acid (RNA)

    Phosphate

    Deoxyribose

    HH

    OH

    OCH2

    Base

    Phosphate

    Ribose

    5M

    OH OH

    o#-ri%$t /$e cGraw"ill o,#anies Inc. 'er,ission re*ired )or re#rod*ction or dis#la-.

    4M 1M

    3M 2M

    5M

    4M 1M

    3M 2M

    OO

    O

    P

    O

    O

    O

    P

    O

    O

    HH HH

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    !igure ".* The structure of nucleotides found in (a) DN and (b) !N

    " #" $ or T

    These atos are 5ound .ithin indiidual nucleotides /o.eer the are reoed .hen nucleotides Goin to*ether to a@e

    strands o5 DNA or RNA

    " #" $ or %

    30

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    Jase su*arnucleoside Eaple

    Adenine ri?ose AdenosineAdenine deori?ose Deoadenosine

    Jase su*ar phosphate(s)

    nucleotide Eaple

    Adenosine onophosphate (A,3)

    Adenosine diphosphate (AD3)

    Adenosine triphosphate (AT3)

    Re5er to Bi*ure 929

    31

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    Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display!igure "."

    &ase al'ays

    attached here

    hosphates are

    attached here

    Adenosine

    Adenosine monophosphate

    Adenosine diphosphate

    Adenine

    Phosphate groups

    Phosphoester bond

    Ribose

    H

    OP CH2

    O

    OO P

    O

    O O O

    O P

    O

    H

    OHHO

    O

    H2M3

    1M4M5M

    Adenosine triphosphate

    NH2

    N

    H

    H

    N

    NN

    32

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    Nucleotides are coalentl lin@ed to*ether ?

    phosphodiester ?onds A phosphate connects the " car?on o5 one nucleotide to

    the $ car?on o5 another

    There5ore the strand has directionalit " to $

    In a strand all su*ar olecules are oriented in the sae

    direction

    The phosphates and su*ar olecules 5or the?ac@?oneo5 the nucleic acid strand The ?ases proGect 5ro the ?ac@?one

    33

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    !igure ".#+

    NH2

    N O

    N

    O

    N O

    N

    Adenine (A)

    Guanine (G)

    Thymine (T)

    BasesBackbone

    Cytosine (C)

    O

    HH

    H

    H

    HH

    OOO

    O

    P CH2

    O

    HH

    H

    H

    H

    HH

    OOO

    O

    P CH2

    O

    NH2

    N

    N

    H

    N

    N

    HH

    H

    HH

    OOO

    O

    P CH2

    O

    NH2

    HN

    N

    N

    H

    N

    HH

    HOH

    HH

    OOO

    O

    P CH2

    OSinglenucleotide

    Phosphodiesterlinkage

    Sugar (deoxyribose)

    Phosphate

    3M

    5M

    5M4M 1M

    2M3M

    5M

    4M 1M

    2M3M

    5M

    4M 1M

    2M3M

    5M

    4M 1M

    2M3M

    CH3

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    In 19"$ Faes ;atson and Brancis Cric@ elucidated

    the dou?le helical structure o5 DNA

    The scienti5ic 5rae.or@ 5or their ?rea@throu*h .as

    proided ? other scientists includin* Linus 3aulin*

    Rosalind Bran@lin and ,aurice ;il@ins Er.in Char*a55

    A Be. e Eents Led to the Discoer o5

    the Structure o5 DNA

    35

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    In the earl 19"0s he

    proposed that re*ions o5

    protein can 5old into a

    secondar structure heli

    Linus 3aulin*

    !igure ".##

    To elucidate this structure

    he ?uilt ?allandstic@odels

    o#-ri%$t /$e cGraw"ill o,#anies Inc. 'er,ission re*ired )or re#rod*ction or dis#la-.

    CC

    C

    CCC

    O

    C

    O

    OC

    O

    H

    H

    H

    H

    N

    CN

    NN

    CC

    CC O

    O

    HH

    NN

    C

    C

    C

    CC

    C

    O

    C

    O

    C

    O

    OC

    O

    H

    HH

    N

    NN

    H

    N

    H

    N

    Carbonyloxygen

    Amidehydrogen

    Hydrogenbond

    (a) An helix in a protein

    36

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    Wet DNA fibers

    X-ray beam

    The pattern represents theatomic array in wet fibers.

    X rays diffractedby DNA

    (b) X-ray diffraction of wet DNA fibers

    Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display

    She .or@ed in thesae la?orator as

    ,aurice ;il@ins

    She used Ora

    di55raction to stud

    .et 5i?ers o5 DNA

    Rosalind Bran@lin

    The di55raction pattern is interpreted(usin* atheatical theor)

    This can ultiatel proide

    in5oration concernin* the

    structure o5 the olecule

    !igure ".#$

    37

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    Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display

    She ade ar@ed adances in Ora di55ractiontechni4ues .ith DNA

    The di55raction pattern she o?tained su**estedseeral structural 5eatures o5 DNA

    /elical

    ,ore than one strand 10 ?ase pairs per coplete turn

    38

    Rosalind Bran@lin

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    Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display

    Char*a55 pioneered an o5 the ?iocheicaltechni4ues 5or the isolation puri5ication and

    easureent o5 nucleic acids 5ro liin* cells

    It .as @no.n that DNA contained the 5our ?ases8

    A - C and T

    Char*a55 analed the ?ase coposition o5 DNA

    isolated 5ro an di55erent species

    Er.in Char*a55s Eperient

    39

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    The /pothesis

    >An analsis o5 the ?ase coposition o5 DNA indi55erent species a reeal iportant 5eatures

    a?out the structure o5 DNA

    Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display

    Testin* the /pothesis

    Re5er to Bi*ure 921$

    40

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    !igure ".#%

    o#-ri%$t /$e cGraw"ill o,#anies Inc. 'er,ission re*ired )or re#rod*ction or dis#la-.

    :#eri,ental level once#t*al level

    ;or eac$ t-#e o) cell etract t$ec$ro,oso,al ,aterial. /$is can bedone in a variet- o) wa-s incl*din% t$e*se o) $i%$ salt deter%ent or ,ild alkalitreat,ent. ote< /$e c$ro,oso,escontain bot$ D( and #rotein.

    1.

    =e,ove t$e #rotein. /$is can be done inseveral wa-s incl*din% trea,ent wit$#rotease.

    2.

    -drol->e t$e D( to release t$e bases)ro, t$e D( strands. ( co,,on wa-to do t$is is b- stron% acid t reat,ent.

    3.

    !e#arate t$e bases b- c$ro,ato%ra#$-.'a#er c$ro,ato%ra#$- #rovides an eas-wa- to se#arate t$e )o*r t-#es o) bases./$e tec$ni*e o) c$ro,ato%ra#$- is

    described in t$e (##endi.

    4.

    :tract bands )ro, #a#er into sol*tionsand deter,ine t$e a,o*nts o) eac$ baseb- s#ectrosco#-. :ac$ base will absorbli%$t at a #artic*lar wavelen%t$. -ea,inin% t$e absor#tion #ro?le o) asa,#le o) base it is t$en #ossible tocalc*late t$e a,o*nt o) t$e base.!#ectrosco#- is described in t$e(##endi.

    5.

    o,#are t$e base content in t$e D()ro, di+erent or%anis,s.

    6.

    !ol*tion o)c$ro,oso,aletract

    D(

    D( @#roteins

    Individ*albases

    Ari%in

    'rotease

    (cid'

    '

    ''' '

    ''

    %%

    % %% %%

    GG G

    G G GG

    G

    G

    G

    %

    %

    %

    -

    41

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    The Data

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    Interpretin* the Data

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    The data sho.n in Bi*ure 921$ are onl a sallsaplin* o5 Char*a55s results

    The copellin* o?seration .as that 3ercent o5 adenine percent o5 thine 3ercent o5 ctosine percent o5 *uanine

    This o?seration ?ecae @no.n as Char*a55s rule It .as a crucial piece o5 eidence that ;atson and Cric@

    used to elucidate the structure o5 DNA

    43

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    Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display

    Bailiar .ith all o5 these @e o?serations ;atsonand Cric@ set out to sole the structure o5 DNA The tried to ?uild ?allandstic@ odels that incorporated

    all @no.n eperiental o?serations

    A critical 4uestion .as ho. the t.o (or ore strands)

    .ould interact

    An earl hpothesis proposed that DNA strands interactthrou*h phosphate,*crosslin@s

    Re5er to Bi*ure 921%

    ;atson and Cric@

    44

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    Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display

    !igure ".#&

    This hpothesis .as o5 course incorrectP

    Copri*ht + The ,c-ra./ill Copanies Inc2 3erission re4uired 5or reproduction or displa2

    !*%ar

    BA

    A A

    A

    '

    ase

    !*%ar

    ase

    !*%ar

    A

    AA

    '

    ase

    !*%ar

    aseAB

    %2@

    45

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    Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display

    The .ent ?ac@ to the ?allandstic@ units The then ?uilt odels .ith the

    Su*arphosphate ?ac@?one on the outside

    Jases proGectin* to.ard each other

    The 5irst considered a structure in .hich ?ases 5or

    / ?onds .ith identical ?ases in the opposite strand ie2 A to A T to T C to C and - to -

    ,odel ?uildin* reealed that this also .as incorrect

    ;atson and Cric@

    46

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    Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display

    The then realied that the hdro*en ?ondin* o5 A toT .as structurall siilar to that o5 C to - So the ?uilt ?allandstic@ odels .ith AT and C-

    interactions ?et.een the t.o DNA strands These .ere consistent .ith all @no.n data a?out DNA structure

    Re5er to Bi*ure 921"

    ;atson Cric@ and ,aurice ;il@ins .ere a.ardedthe No?el 3rie in 19! Rosalind Bran@lin died in 19"& and No?el pries are not

    a.arded posthuousl

    ;atson and Cric@

    47

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    (b) Original model of the DNA double helix

    (a) Watson and Crick

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    arrin%ton rownC'$oto =esearc$ers

    *lton(rc$ive b- Gett- I,a%es

    !igure ".#' 48

    The DNA Dou?le /eli

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    Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display

    -eneral structural 5eatures (Bi*ures 921 Q 921')

    The DNA Dou?le /eli

    > 6n our 6.n

    T.o strands are t.isted to*ether around a

    coon ais

    There are 10 ?asesand $2% n per coplete turno5 the heli

    The t.o strands are antiparallel

    6ne runs in the " to $ direction and the other $ to " The heli is ri*hthanded

    As it spirals a.a 5ro ou the heli turns in a

    [email protected] direction

    49

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    Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display

    -eneral structural 5eatures (Bi*ures 921 Q 921')

    The DNA Dou?le /eli

    The dou?le?onded structure is sta?ilied ?

    12 /dro*en ?ondin* ?et.een copleentar ?ases A ?onded to T ? t.o hdro*en ?onds

    C ?onded to - ? three hdro*en ?onds

    !2 Jase stac@in* ;ithin the DNA the ?ases are oriented so that the 5lattened

    re*ions are 5acin* each other

    50

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    Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display!igure ".#(

    Copri*ht + The ,c-ra./ill Copanies Inc2 3erission re4uired 5or reproduction or displa2

    H

    N HN

    N

    N

    G

    NH2

    H

    P

    S

    P

    SP

    5end

    3end

    H NH2

    N

    N

    HH

    H

    HH

    OOO

    O

    P CH2

    O

    HH

    H

    OH

    HH

    OOO

    O

    P CH2

    O

    HH

    H

    HH

    OOO

    O

    P CH2

    O

    CH2

    HH

    H

    HH

    OOO

    O

    P

    O

    T

    ey Feat"re*

    Two strands of DNA form aright-handed double helix.

    The bases in opposite strandshydrogen bond according to the

    AT/GC rule.

    The 2 strands are antiparallel withregard to their 5 to 3 directionality.M M

    There are ~10.0 nucleotides in eachstrand per complete 360 turn ofthe helix.

    2 nm

    One nucleotide0.34 nm

    One completeturn 3.4 nm

    TA

    G C

    T AP

    P

    P

    P

    P

    S

    S

    S

    S

    S

    S

    S

    S

    S

    A

    C

    G

    C G

    C G

    G C

    G C

    GC

    G C

    C

    P

    P

    S

    P

    PP

    P

    P

    S

    SS

    S

    S

    P

    P

    P

    P

    P

    P

    P

    P

    P

    P

    S

    S S

    S

    S

    S

    S

    S

    SP

    S

    S

    P

    P

    P

    S

    S

    S

    SP

    3

    5

    G

    S

    35

    S

    A

    P

    P

    C

    T A

    O

    N

    N

    N

    NA

    H

    H NH2

    N

    O

    H

    N

    CH3

    H

    T

    H

    HH2N

    N

    N C

    O

    3end

    5end

    H

    H

    HH

    OOO

    O

    PCH2

    O

    H

    H

    H

    H

    HH

    OOO

    O

    PCH2

    O

    H

    H

    HH

    OOO

    O

    PCH2

    O

    H

    H

    HH

    OOO

    O

    PCH2

    O

    HO

    N

    O

    H

    N

    CH3

    H

    T

    O

    NH N

    N

    N

    G

    H2N

    H

    H

    H

    N

    N

    N

    N A

    H

    H2N H

    "

    "

    "

    "

    "

    "

    "

    "

    ""

    51

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    Copyright The McGraw-Hill Companies, Inc. Permission required or reproduction or display

    -eneral structural 5eatures (Bi*ures 921 Q 921')

    The DNA Dou?le /eli

    There are t.o asetrical *rooeson the

    outside o5 the heli 12 ,aGor *rooe

    !2 ,inor *rooe

    Certain proteins can ?ind .ithin these *rooes The can thus interact .ith a particular se4uence o5 ?ases

    52

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    (b) Space-filling model of DNA(a) Ball-and-stick model of DNA

    Minorgroove

    Majorgroove

    Minorgroove

    Majorgroove

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    Ea%*na Desi%nC'$oto =esearc$ers

    !igure ".#) 53

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    54

    /o calc*late $ow o)ten t$e en>-,e willc*t