Transcript
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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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