Final review
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| Replication fidelity | Proofreading activity to remove incorrectly paired nucleotides. mismatch repair(MMR)-corrects errors after replication is complete
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| Differences between Eukaryotic and Bacterial replication | origin contain autonomously replicating sequences(ARS) to initiate DNA replication.orignin recognition complex binds to ARS to initiate DNA replication.DNA replication becomes liscensed by MCM helicase
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| MCM helicase | mini chromosome maintenance
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| The DNA polymerases in Eukaryotes | delta, episalon,alpha
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| Telomere hypothesis | repetive sequences at end of chromosome.get shorter as cell divides. circular DNA does not have this problem.
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| Telomerase | reverse transcription.ca lengthen but can never synthesize the very end.has protruding end w/G rich repeated sequence.nucleotides added 3'end of G-rich strand.after several nucleotides added,moves over.
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| Polymorphism | (SNP).is a genetic change that is present in >1% of the population.
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| Exogenous (external) sources | uv light, ionizing radiation, chemical mutagens
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| Endogenous(internal) sources | DNA replication errors, reactive oxygen species,programmed DNA breaks (meiosis, antibody generation)
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| Mutagen | a physical or chemical agent that signifantly increases the frequency of mutational event
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| Carcinogen | natural/ artificial agent that increases frequency of cancer
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| Main types of DNA damage | strand break,base mismatches, chemical adducts
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| strand break | cut in sugar phosphate backbone
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| chemical adducts | chemicals attached to base/backbone
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| Gene mutation. point mutations examples | base changes. deletions, insertions
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| Chromosomal rearrangements | deletions, insertions, inversions, translocations
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| consequence of unrepaired DNA damage... (DNA relation) | change in sequence, change of reading frame, breakage or loss of chromosome
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| Consequence of unrepaired DNA damage... (protein relation) | altered protein production. altered protein function, loss of protein function
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| Missense mutation | change of seqence that codes for a different AA
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| Silent mutation | change in codon, but codes for the same AA
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| Neutral mutation | change in codon, but codes for an AA with similar biochemical properties.SmAA to SmAA.negAA to negAA. hydrophobic AA to hydrophobic AA.
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| Frame shift mutation | change of sequence that shifts the reading frame, changing the subsequent codon
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| nonsense mutation | change of sequence that introduces a stop codon
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| Consequence of unrepaired DNA damage...(tissue/organ relation). | altered/ loss of function. disease when affects entire organism. aging. death
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| somatic mutation | non reproductive cells. only regional
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| germ line mutation | in cells that give rise to gametes.affects entire body
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| UV light damge | causes thymine dimers.nucleotide excision repair.if two thymines next to each other they can covalently bond.physically attached to each other.polymerase gets stuck and cant go any further.no transcription past dimer.cytosine too.
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| oxidative stress from cellular metabolism | creates ROS(reactive oxidative stress).oxygen comes from reactive oxygen from cellular respiration.ex:8-oxoguanine
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| 8-oxoguanine | extra oxygen at position 8.binds with adenine. guanine normally pairs with cytosine. changes sequence from GC to AT if not repaired.
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| DNA replication errors that create mismatches | misincorporation/mispairing.DNA slippage
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| Misincorporation/mispairing | wrong pair at one base
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| DNA slippage | repetitive sequence makes it hard to know exactly where to bind.causes insertion or deletion based on loops that develop
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| How is DNA damage fixed to avoid mutation? | redudancy,percision of cellular replication machinery.DNA repair
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| Three major steps in repair | damage recognition, Damage removal, synthesis of new DNA.
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| damage recognition | each type of damage has its own missmatuch mut.
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| Damage removal | exonuclease or endonuclease
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| Synthesis of new DNA | DNA polymerase and ligase to fix back bone
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| excision repair fixes what two types of damage? | Thymine dimers and oxidative DNA damage.
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| What are the two types of excision repair? | nucleotide exision repair and base exicision repair
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| Nucleotide exision repair | NER.removes bulky DNA lesions that disort the double helix.DNA is separated and bound SSBS.Nuclease cleaves the stand on both sides of the damage.damage strand is removed.gap is filled in by DNA polymerase and ligase.fixes uv light damage
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| Base excision repair(BER) | excises modified bases and then replaces entire ncleotide.DNA glycosylase cuts base out but leaves backbone. abasic site(AP).AP endonuclease cuts backbone.DNA polymeraes brings in correct base w/backbone.
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| Mismatch repair | (MMR).Repairs DNA polymerase errors.MSH2(muts) finds missmatich.MSH2 brings in MutL to bind to muts and transmits signals to enzymes that are going to repair.one strand is methylated
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| Human disease associated with defective DNA repair | NER-deficiency-xp:caused by defective nucleotide excision repair.
MMR deficieny-hereditary nonpoltposis
HNPCC-caused by DNA mismatch repair.mutations in 50%MLH,40% MSH2, 10%MSH6.
Huntingtons
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