Chap 16 Nucleic Acid

7/31/2019 Chap 16 Nucleic Acid

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Standard Questions 1

1. What is the central dogma?2. How is DNA damaged?

3. What historical dvelopments

led to the discovery of DNAstructure?

4. What information did Watsonand Crick use to determine

DNA structure?5. What are the structural

differences among A-DNA, B-DNA, H-DNA and Z-DNA?

6. What is the structuralsignificance of DNAsupercoiling?


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Standard Questions 2

1. What are nucleosomes?2. What are the three most

prominent forms of RNA?

3. What properties of virusesmake them useful researchtools for biochemists?

4. What type of genomes can

viruses possess?5. What is the differences

between lytic and lysogenicviruses?

6. After many years of researchand billions of dollars spent,why is AIDS still consideredan incurable disease?


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Central Dogma of Molecular Biology


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INFORMASI GENETIK

Dalam bentuk Deoxyribose NucleicAcid (DNA)

Tersusun dalam rantai double helix

Basa Nukleotida penyusun DNA hanya

terdiri dari empat basa nukleotida yaitu

Adenin (A), Guanin (G), Cytosin (C),

dan Thimin (T)

Informasi genetik ini terletak pada

genome inti (Kromosom) dan

genome sitoplasma (mitokondria)

pada manusia dan hewan, sedangkan

pada tanaman berada pada genome

inti (kromosom) dan genom

sitoplasma (kloroplas dan

mitokondria).


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STRUKTUR DNA


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STRUKTUR DNA


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CIRI DNA

Anti paralelisme

yaitu suatu sekuen DNA yang terbentuksecara berpasangan (double stranded)memiliki pola yang saling berlawananarahnya dari masing-masingkomplemennya, namun polanya sama yaitu

dari 53.Komplementarisme

yaitu suatu sekuen DNA yang terbentuksecara berpasangan (double stranded)

memiliki pola pasangan yang tetap (A vs Tdan C vs G).

Denaturasi

yaitu apabila DNA dipanaskan akanmengalami perubahan konformasinya

dengan lepasnya ikatan yangmenghubungkan masing-masing fragmendan pada suhu > 90oC akan berubah dariutas ganda menjadi utas tunggal.


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STRUKTUR DNA

Tersusun dalam rantai double helix

Untaian polinukleotida salingberpasangan menyusun untai tersebut.

Basa Nukleotida penyusun DNA hanyaterdiri dari empat basa nukleotida yaituAdenin (A), Guanin (G), Cytosin (C),dan Thimin (T)

Pasangan komplementer dari basa-basanukleotida tersebut adalah :

- Adenin (A) berpasangan dgn Thimin

(Basa Purin)- Guanin (G) berpasangan dgn Cytosin(Basa Pyrimidin).


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Two Models of DNA Structure


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DNA Structure


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A Tautomeric Shift Causes a

Transition Mutation


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Base Modification


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Thymine Dimer

Structure


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Intercalating Agents

(antimalaria & intestinal

tapeworms)


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X-Ray Diffraction Study

of DNA by RosalindFranklin & R. Gosling


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INFORMASI GENETIK

Hasil sekuensi urutan DNA


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STRUKTUR DNA

5 A A A G C C T G G G G T G C C ---

3 T T T C G G A C C C C A C G G --


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CIRI KHUSUS DNA


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REPLIKASI DNA

Oleh karena DNA terdiri darifragmen yang berpasangan makasetiap utas DNA asal akan berperansebagai template (materi dasar) untukreplika berikutnya.

Pemecahan yang paling mudahdalam pemisahan dari utas ganda ke

utas tunggal adalah lepasnya ikatanhidrogen diantara dua utas tersebut.

Setiap utas tunggal yang telahterpisah tersebut akan berpasangan

dengan utas komplementer dari hasilreplika yang baru untuk menggantikanpasangannya yang memisah.


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REPLIKASI DNA

Replikasi DNA terjadi secara mekanisme

Semikonservatif . Proses replikasi ini

dikemukakan oleh Watson dan Crick. Hal

ini kemudian telah diverifikasi oleh

Meselson dan Stahl.

Mekanisme replikasi konservative adalah

bila Seutas DNA awal akan menggandakan

diri dengan cara memisahkan utas gandamenjadi utas tunggal dan masing-masing

utas tunggal tersebut akan bertindak sebagai

templeta bagi duplikasi proses

berikutnya.Setiap utas tunggal yang telahterpisah tersebut akan berpasangan dengan

utas komplementer dari hasil replika yang

baru untuk menggantikan pasangannya yang

memisah.


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REPLIKASI DNA MERUPAKAN PROSES

YANG SANGAT KOMPLEKS

Merupakan proses penggandaanmirip dengan pabrikasi.

Melibatkan beberapa enzim yang

sangat spesifik, seperti enzimpolymerase dll.

Sintesis selalu berjalan dengan arahdari 5 ke 3

Sintesis DNA memerlukan suatuRNA primer. RNA primer inidisintesa pada tempat dimana replikasidimulai.

Prosesnya terjadi secara leadding &lagging

Berlangsung secara bidirectional

(dua arah).


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ENZIM-ENZIM YANG TERLIBAT DALAM

REPLIKASI DNA

Macam Enzim FUNGSINYA

. DNA

Helicase

Membuka double helix

dengan memecahkan ikatan

hidrogen

.

Topoisomerase

Memecahkan satu atau dua

utas DNA dan

melindunginya dari excessi

coiling dan melekatkan lagi

. DNA

Polymerase

Menyambungkan secara

berurutan basa-basa yang

diperlukan

. DNArimase

Mensintesa primer RNA ygpendek

. DNA ligase Menyatukan kembali antara

untai 5 dengan untai 3

. Telomerase Menguatkan DNA telomerik


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KARAKTER RNA

Basa Nukleotida penyusunRNA hanya terdiri dari empat

basa nukleotida yaitu Adenin

(A), Guanin (G), Cytosin (C),dan Urasil (U)

Gula penyusunnya berupa

Ribose


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MACAM-MACAM BENTUK RNA

2. Ribosomal RNA atau rRNA

3. Transfer RNA atau tRNA

1. Messenger RNA atau mRNA


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A-DNA, B-DNA, & Z-DNA


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CruciformsCruciforms form because of palindrome

sequences


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H-DNA(a).DNA sequence with long segments such as (A-G)n bonded to (T-C)n can

form H-DNA. (b).H-DNA formation depends on the formation of

nonconventional (Hoogsteen) base pairing


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Linear and Circular DNA

and DNA Winding


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Supercoilsa. Toroidal, b.interwound


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The E. Coli

Chromosome


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Chromatin and Nucleosome


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Chromatin


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Chromatin


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Secondary Structure of RNA


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Transfer RNAa.Three-dimensional structure of a tRNA molecule, b.A tRNA

molecule


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rRNA Structure


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Viral Lifestyles

Basic steps in the life cycle of

all viruses :1. Infection :

Penetration of the virion or itsnucleic acid into the host cell

2. Replication :Expression of the viral genome

3. Maturation : Assemblyof viral components into

virions4. Release :

The emission of new virionsfrom the host cell

Viruses must exploit some ofthe normal metabolic reactionsof its host cell to complete thelife cycle


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Bacteriophage T4

Lifestyle

1. Adsorbing the virion to the surfaceof an E. Coli cell

2. The DNA is injected by flexing andconstricting the tail apparatus(transduction) (Infection iscomplete)

3. Synthesis of host DNA, RNA, andprotein stops

4. Begin phage mRNA synthesis

5. Phage mRNA codes for the synthesisof capsid proteins and some of the

enzymes required for thereplication of the viral genome(replication is complete)

6. Assembly of virion components

7. Other enzymes are synthesizedthat

weaken the host cells cell wall, sothat new phage can be released fornew rounds of infection (maturationis complete)

8. The virion is released and infectnearby bacteria, thus initiating new

infections (release is complete)


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The T4 Bacteriophage


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Life Cycle of the T4

Bacteriophage


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Terminology

Virulent : bacteriophage that

initiate lytic cycle and destroytheir host cells

Lytic : a condition in which the

phage destroy their host cells

Lysogeny : a condition in whichthe phage genome (prophage) is

copied along with host DNA

during cell division for an

indefinite period of time


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H I V The causative agent of AIDS

An enveloped virus that belongs tounique group of RNA viruses calledthe retrovirus

Retroviruses : contain an enzymaticactivityreverse transcriptase( synthesizes a DNA copy of assRNA genome )

Contain several enzymes : reversetranscriptase, ribonuclease,

integrase, and protease The RNA molecules are coated withmultiple copies of two low-molecular-weight proteins : p7 andp9

The bullet-shaped core is composedof hundreds of copies of p24

The envelope contains two majorviral proteins : gp120 and gp41


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HIVThe human immunodeficiency virus


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HIV Lifestyle HIV infection :

Direct exposure of an individuals bloodstream tothe body fluids of an infected person e.g : sexualcontact, blood transfusions, and perinataltransmission from mother to child

HIV enters the body infect T-4 helperlymphocytes of the immune system cells formCD4 antigen on T cells plasma membranesgp120-CD4 complex with a chemokine receptorthe viral envelope fuses with the host cells plasmamembranes the two RNA strands are releasedinto cytoplasm reverse transcriptase catalyzesthe synthesis of a ssDNA using the vRNA as atemplatethe heterodimers RNaseactivitydegrades the vRNA the same proteinproduces a double-strand vDNA by forming acomplementary strand of the ssDNA Viralintegrase integrates the vDNA into a host cellchromosome The proviral DNA remains latentuntil the specific infected T cell is activated. Theproviral DNA direct cell to synthesize viralcomponents Newly synthesizedviruses bud

from the infected cell, eventuallyHIV-infected cellsdie.

The CCR5 receptor helps HIV enter T cellsCXCR4 receptor is used (humans with two copiesof defective CCR5 gene are resistent to HIVinfection)


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Mechanism of HIV-

infected cells die

1. The budding of a virus fromthe cell membrane may tearthe membrane and causemassive leakages that cannot

be repaired2. Massive release of new virus

from a cell, directed by theprovirus, may so deplete the

cell that it disintegrates3. The bindng of cell surface

gp120 molecules to CD4receptors on nearby healthycell leads to formation oflarge, nonfunctionalmultinucleated cell massescalled syncytia


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AIDS

Initial symptoms : fever, lethargy, headache,

and other neurological complaint, diarrhea,and lymph node enlargement

ARC (AIDS-related complex)

The individual becomes susceptible to seriousopportunistic diseases to have developedAIDS

2 10 years for AIDS development AIDS-related diseases :pneumocystis cariniipneumonia, cryptococcal meningitis,toxoplasmosis (brain lesions, heart and kidneydamage, and fetal abnormalities),cytomegalovirus infections (pneumonia,kidney and liver damage, and blindness),

tuberculosis, skin cancer (Kaposis sarcoma) Treatment : suppress symptoms (e.g.,

antibiotics for infections) and slow viralreproduction (azidothymidine AZT is anucleotide base analog that inhibits the vDNAsynthesis catalyzed by reverse transcriptase;indinavir is the protease inhibitors that

prevent processing of viral protein) Developing an AIDS vaccine is difficult,

because the viral genome mutates (changes inthe chemical composition of theenvelope)frequently


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Representative Virusesa.Pox virus, b.rhabdovirus, c.mumps virus, d.flexible-

tailed bacteriophage, e.herpes virus, f.papilloma virus


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Thank you!See you later...!!

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Chap 16 Nucleic Acid