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CHAPTER 8CHAPTER 8THE REPLICATION OF DNA 王青 200432290064 生物科学类
OUTLINEOUTLINE
• DNA polymerization • DNA replication • Action of Telomerase
DNADNA polymerizationpolymerization
•1.The Chemistry of DNA Synthesis
•2. The Mechanism of DNA Polymerase
•3. The Replication Fork
The Chemistry of DNA SynthesisThe Chemistry of DNA Synthesis
• deoxynucleoside triphosphates• primer:template junction• primer• Hydrolysis of pyrophosphate (PPi)• Metal ion
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The Mechanism of DNA PolymeraseThe Mechanism of DNA Polymerase
Thumb
Palm
Fingers
palmpalm
•Palm domain hydrogen bonds to base pairs in minor groove
•Hydrogen bonds only form if nucleotides are correctly base paired
Fingers Fingers
•Finger domain associates with template region
•90 。 turn of template helps avoid confusion in the active site
ThumbThumb
•Holds the primer:template junction in the active site
•Reduces the rate of dissociation
• Exonucleases proofread newly synthesized DNA
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Replication fork
DNA replicationDNA replication
• 1. The Specialization of DNA Polymerases
• 2. DNA Synthesis at the Replication Fork
• 3. Initiation of DNA Replication
Th
e re
plic
atio
n
fork
Leading strand
Lagging strand
Okazaki fragment Replication fork
•Need the help of DNA pol ,DNA helicase, SSB, primase, DNA topoisomerase
DNA helicse
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SSB
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DNA topoisomerase
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• DNA Pol III holoenzyme, helicase and primase interact with each other to form replisome, a finely tuned factory for DNA synthesis with the activity of each protein is highly coordinated.
replisomereplisome
• the trombone model for coordinating replication by two DNA polymeraes at the repolication fork
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Three differentfunctions of initiator protein: (1) binds to replicator, (2) distorts/unwinds a region of DNA, (3) interacts with and recruits additional replication factors
Action of TelomeraseAction of Telomerase
• 1. Binding and Unwinding: origin selection and activation by the intiator protein
• 2. Finishing Replication
Telomere replicationTelomere replication
The end of linear chromosomes can’t be fully replication by semi-discontinuous replication as there is no DNA ti elongate to replace the RNA removed from the 5’-end of the lagging strand. Thus,genetic information sould be lost from the DNA. To over come this, the ends of eukaryotic chromosomes( telomeres) consist of hundreds of copies of a simple, noninformational repeat sequence with the 3’-end overhanging the 5’-end.
The enzyme telomerase contains a short DNA molecule part of whose sequence is complementary to this repeat. This RNA acts as a template for the addition of these repeats to the 3’-overhang by repeated cycles of elongation and translocation
Repulication of telomeres by tRepulication of telomeres by telomerase(FIGURE 8-36)elomerase(FIGURE 8-36)
• Telomerase uses its RNA component to the 3’-end of the ssDNA region of the telomere.
• Telomerase then uses its reverse transcription activity to synthesize DNA to the end of the RNA template.
• Telomerase then displaces the RNA from the DNA product and rebinds at the end of the telomere and repeats the process
Role of Telomeres and Role of Telomeres and Telomerase in Cancer and Telomerase in Cancer and
AgingAging
G1
G2M
S
G0
• G1 :the longest phase during which the cells are preparing for DNA replication
• S: the only period in the cell cycle during which DNA is replication
• G2: a short gap before mitosis• M: mitosis and cell division
• G0: cell can also exit the cell cycle after mitosis and enter a nonprotiferative state
THANK YOUTHANK YOU