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61 Cards in this Set
- Front
- Back
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Point mutation
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Exchanges a single base for another.
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Point mutation: transition
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Exchanges a purine for a purine, or a pyrimidine for a pyrimidine.
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Point mutation: transversion
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Exchanges a purine for a pyrimidine. Rarer than transition mutation.
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Insertion mutation
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Adds one or more nucleotides to DNA sequence.
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Deletion mutation
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Removes one or more nucleotides from DNA sequence.
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Tautomers can confuse DNA polymerase during replication; what are the tautomers for amino and keto groups?
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amino: imino
keto: enol These fit in the double helix but hydrogen bond differently than the normal bases. |
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Mismatch mutation is caused by ...
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tautomers of the bases being added and not recognized by DNA polymerase.
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Two forms of spontaneous DNA damage
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Deamination
Depurination |
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Deamination mutation
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Cytosine degrades to uracil by hydrolysis, releasing ammonia
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Does deamination permanently impair the DNA molecule?
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No - deamination can be repaired by DNA polymerase.
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What is the function of the beta-glycosidic bond?
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It binds the base to the sugar.
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What process breaks the beta-glycosidic bond between a base and a sugar?
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hydrolysis
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Depurination
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The beta-glycosidic bond between base and sugar in a purine is cleaved by hydrolysis, and the purine drifts away.
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Chemical mutagens most often cause a mutation in the ... of the nucleotide.
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base
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Ultraviolet light causes ... in stacked pyrimidines in DNA.
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dimerization
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A kink in DNA is caused by same-strand dimers, induced by ...
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UV light
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What is the relative accuracy of DNA polymerase?
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10e-6, or 1 in 1,000,000
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Overall fidelity of replication
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10e-10, or 1 in 10,000,000,000
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The disparity between DNA's natural accuracy and the *actual* fidelity is due to ...
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the mismatch repair system
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How is the parent strand discriminated from the daughter strand?
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The parent strand is methylated.
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Finds, excises, and replaces mispaired bases in the daughter strand from replication.
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Mismatch repair system
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What enzyme methylates newly replicated strands of DNA?
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Dam methylase
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What is the function of Dam methylase?
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Methylates newly synthesized strands of DNA
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UvrD is what kind of molecule?
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helicase
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Mismatch Repair
MutS recognizes mismatch, and binds to it. MutS recruits MutL for help, and they form a complex. The MutS-MutL complex recruits MutH. MutH binds to the closest hemi-methylated site. MutL and MutH attract each other like magnets, bending the strand until they touch. The triple complex makes a nick at the nonmethylated site of the hemimethylated area. Exonuclease then starts chomping, going along the strand until it reaches the mismatch (and a ways beyond). DNA polymerase III then fills in the newly empty portion, and DNA ligase seals it. Dam methylase then methylates the previously unmethylated daughter strand. |
Mismatch Repair
MutS recognizes mismatch, and binds to it. MutS recruits MutL for help, and they form a complex. The MutS-MutL complex recruits MutH. MutH binds to the closest hemi-methylated site. MutL and MutH attract each other like magnets, bending the strand until they touch. The triple complex makes a nick at the nonmethylated site of the hemimethylated area. Exonuclease then starts chomping, going along the strand until it reaches the mismatch (and a ways beyond). DNA polymerase III then fills in the newly empty portion, and DNA ligase seals it. Dam methylase then methylates the previously unmethylated daughter strand. |
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What is the eukaryotic homolog of MutS?
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hMSH2
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What is the eukaryotic homolog of MutL?
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hMLH1, hPMS1, hPMS2
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What is the order of protein recruitment in the mismatch repair system? (7 proteins)
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MutS -> MutL -> MutH -> exonuclease -> DNA Pol III -> DNA ligase -> Dam methylase
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In mismatch repair, ... and ... attract each other like magnets, bending the DNA strand.
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MutL and MutH
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In mismatch repair, where is the first nick made in the DNA strand, and what makes it?
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At the hemimethylated site; the triple complex of MutS-MutL-MutH
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Which polymerase fills the excised area in the mismatch repair system?
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DNA Pol III
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What is the enzyme that methylates new strands of DNA
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Dam methylase
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What is the role of MutS in the mismatch repair system?
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It recognizes the incorrect base, and recruits MutL.
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Mismatch repair in eukaryotes is poorly understood; what is the leading theory for strand discrimination?
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Believed to rely on the presence of Okazaki fragments.
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glycosylase (purpose)
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Cleaves glycosidic bond between base and sugar
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Cytosine deaminates to ...
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uracil
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Uracil arises from ...
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deamination of cytosine
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Deamination of adenine produces ...
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hypoxanthine
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Hypoxanthine arises from ...
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deamination of adenine
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DNA glycosylases ... and ... abnormal bases in base excision repair.
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recognize and remove
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Alkylated base recognize by DNA glycosylase in base excision repair
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7-methylguanine
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In base excision repair, a pyrimidine dimer will be ...
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recognized as abnormal and excised.
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What's the difference between cytosine and uracil?
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Cytosine has -NH2 (aminated) and uracil has =O (deaminated)
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What's the difference between adenine and hypoxanthine?
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Adenine has -NH2 (aminated) and hypoxanthine has =O (deaminated)
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UV light causes dimerization in ...
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neighboring pyrimidines
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In base excision repair, abnormal bases are cut by ...
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AP endonuclease
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AP in AP endonuclease stands for ...
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apurinic / apyrimidinic; the endonuclease cuts at an apurinic site
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What replaces the cut DNA fragment in base excision repair?
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DNA Pol I
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Why does DNA have thymine instead of uracil?
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Because U (in DNA) is always out of place; if C -> U, and U were normal, the repair systems wouldn't know which U was the bad one.
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Difference between thymine and uracil
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Thymine has an extra methyl group.
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Difference between thymine and 5-methyl cytosine
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5-methyl cytosine is aminated where thymine has =O; otherwise identical
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What is the significance of the structural similarity between thymine and 5-methyl cytosine?
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"Hotspot" for mutation
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C-G -> U-G
What happens? |
Cytosine has deaminated to uracil, and will be recognized by uracil glycosylase.
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C(5-Me)-G -> T-G
What happens? |
5-methyl cytosine has deaminated to thymine, and DNA repair systems do not know if the T is incorrect or if it's the G.
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How does the body deal with the ambiguity involved in a G-T mismatch?
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Removes thymine. Repair system assumes the T arose from a deaminated 5-MeCyt.
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Describe the overall process of nucleotide excision repair.
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Occurs when bulky lesion in strand is found; involves over 16 polypeptides. Nicks the strand on either side of the lesion and replaces the segment.
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Difference between GGR (global genome repair) and TCR (transcription-coupled repair)
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GGR recognizes a lesion in a completed strand; TCR recognizes the lesion during the process of transcription (uh-oh, we've hit a bump!)
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GGR
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Global genome repair
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TCR
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transcription-coupled repair
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3 diseases caused by defects in nucleotide excision repair system
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xeroderma pigmentosa
Cockayne's syndrome Trichothiodystrophy |
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Are particular lesions exclusive to repair systems?
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No - there is considerable overlap to make sure lesions are repaired.
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