Lecture+16 (10) - Lecture16 SYSTEMS BIOLOGY Network...

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Lecture 16:  Gene Mutation and Repair
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SYSTEMS BIOLOGY Network analysis: - nodes = proteins, genes, promoters, metabolites - edges = interactions between nodes
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Personal Genomics Called back to Africa by DNA http://www.latimes.com/news/local/la-me-africa18-2009feb18,0,7369816.story
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-Ethics? -Health care? -Do you want to know? -Understanding association studies..
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LECTURE 16 Outline: REVIEW: The replication fork Mutations Types of mutation Mechanisms of spontaneous mutation Induced mutation Consequences of mutation DNA repair Repair mechanisms, damage tolerance Double-stranded break repair - homologous recombination - non-homologous end-joining
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1) Initiation 1) Unwind strands 1) Polymerize 1) Clean up and connect DNA Replication
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The Replication Fork Helicase strand separation Primase RNA primer synthesis Single-stranded binding protein ssDNA stabilization DNA polymerase III + clamp DNA synthesis Also: DNA pol I, ligase
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Replication Initiates at Multiple Origins in Eukaryotes
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LECTURE 16 Outline: REVIEW: The replication fork Mutations Types of mutation Mechanisms of spontaneous mutation Induced mutation DNA repair Repair mechanisms, damage tolerance Double-stranded break repair - homologous recombination - non-homologous end-joining
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Most mutations A) cause loss of gene function B) cause gain of gene function C) are recessive D) are dominant E) both A and C
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Most mutations A) cause loss of gene function B) cause gain of gene function C) are recessive D) are dominant E) both A and C
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Mechanisms of spontaneous mutation 1) Transposon insertions - not covered in class 1) Indels caused by slippage during DNA replication 1) Replication errors causing base substitution 1) Chemical changes in bases
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2) Replication Slippage: a source of indel mutations Thus, short repetitive sequences (microsatellites) are “hotspots” for indel mutations Figure 15.10
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Repeat expansion is the cause of a number of neurological disorders
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3) Replication errors Base replacement : rare base tautomers can mispair Figure 15.8
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4) Base damage by deamination U pairs with A so: C-G to T-A transition G-C to A-T transition T pairs with A so: C-G to T-A transition G-C to A-T transition
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