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23 Cards in this Set
- Front
- Back
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genetic code |
how DNA sequence translates to aas via mRNA -codons -AUG (met): start codon (can also be w/n protein sequence) -UAA, UGA, UAG: stop codon, no aa 61/64 codons code for aas *can be written as DNA/RNA |
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reading frame in translation |
-3 base code=3 possible reading frames -proteins start when first AUG (from 5' end) encountered on mRNA --> establishes reading frame all the way until stop codon |
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protein start and stop site vs. transcription initiation and termination site |
protein start = AUG -downstream from mRNA 5' end=transcription initiation site protein stop -upstream from mRNA 3' end=transcription termination site |
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Mutation types |
1. Point - single base change a. silent- same aa b. missense- changes aa c. nonsense- creates premature stop codon 2. insertion/deletion -addition/loss of 1+ bases -results in frameshift if not multiple of 3 |
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usual cause of genetic disease |
mutations: inherited or spontaneously acquired |
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Sickle cell disease |
Missense mutation: 6th codon of ß globin gene -acidic residue (glu) --> phobic residue (val) ----> polymerization of α2ß2 Hb molecule when deoxy --> sickling RBCs --> occlude capillaries --> severe pain |
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Thalassemia syndromes |
reduced amounts (α+, ß+) or no normal activity (α0, ß0) of α and ß globin proteins Nonsense mutation : shortened protein that does get made has zero activity of nrmal function--> normal Hb (α2ß2) complex isn't made --> severe anemia (small, pale, misshapen RBCs) and life-threatening symptoms |
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frameshift mutations |
-often bring in new stop codons downstream of insertion/deletion site --> translated protein w/ more or less amount of incorrect sequences --> 0-100% of wt activity |
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sources of mutation |
1. DNA replication errors that remain uncorrected 2. base change/alteration/damage not related to replication errors -Spontaneous base alteration at high rates -env. can damage DNA (solar radiation, food chemicals, water, air) |
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Mismatch Repair (MMR) |
-newly synthesized strand (linked temporally to DNA rep) --> last chance for fidelity -MSH proteins (2,6) recognize mismatch -->MLH1/PMS2 endonucleases cut DNA on either side of mismatch --> leaves 3'OH and 5'P --> combined helicase/exonuclease action cleaves DNA portion containing mismatch --> DNApol (replisome-associated polymerases=how old and new strand are distinguished) resynthesizes DNA in gap --> DNA ligase closes -fails 1/10^2 nucs |
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overall error rate upon completion of DNA rep (post proof-reading and MMR) |
1/ 10^9-10^10 nnucleotides |
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mutations that cause altered/loss of function of MLH or MSH proteins commonly associated w/? |
cancer |
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Defects in DNA metabolism genes (e.g. DNA repair) |
often cancer causing: genome-wide DNA sequence changes (mutations) become common because not repaired when replication errors occur --> loss/gain of function in that protein -critical cell proliferation control genes may become mutated --> loss of control of cell prolif = hallmark of cancer |
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Lynch Syndrome |
Hereditary Non-polyposis Colorectal Cancer (HNPCC) -MSH or MLH-type genes mutated and non-functional --> defective MMR -1 copy inherited from mother, 1 from father -autosomal dom -onset usually before age 50 Men w/ lynch: 80% risk for colorectal (colon) cancer Women w/ lynch: 60 % risk for colorectal, 60% risk for endometrial |
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spontaneous base hydrolysis |
deamination: -occur hundreds of times/day - C hydrolyzed --> U (bps w/ A instead of C) depurination: -occur thousands of times/day -G hydrolyzed --> apurinic site in DNA (just sugar and phosphate remain) |
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Base Excision Repair (BER) |
-mechanism for correcting spontaneous base hydrolysis= deamination and depurination (and other base changes - oxidation of G) -DNA glycosylases: many different species which eliminate specific bases/alterations --> apurinic or apyrimidinc site --> AP endonuclease and phosphodiesterase cut 5' side --> elimination of sugar 5' phosphate residue --> DNApol ß (special repair pol in humans) adds correct nuc --> ligase seals |
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Smoking |
results in DNA adduct to guanine --> still recognized as G during replication? benzo[a]pyrene detox --> addition of adduct to G |
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UV-A and UV-B (solar radiation) |
causes thymine dimers -sunscreen works |
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Nucleotide Excision Repair (NER) |
damage recognized --> endonucs cut on either side of damage --> helicase, exonucleases remove damaged DNA and form gap --> DNA pol I (ß) fill gap --> ligase seals |
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post-DNA replication repair processes (spontaneous errors) |
1. NER 2. BER |
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DNA replication associated error repair processes |
1. proofreading 2. MMR |
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Cisplatin (CDDP) |
-cross-links DNA -> stand breaks during DNA replication -takes advantage of rapid proliferation f many tumors -used in treating many tumor types (cervical, testicular, lung cancer) -study: more adducts post-therapy = better survival % |
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Xeroderma Pigmentosum (XP) groups A-G |
phenotype: -skin cancer (1000x risk, <20yrs), UV sensitivity, neurological ab, excessive freckling, hyperpigmentation -non-melanoma skin cancer median age=8 yrs -inherited NER mutation: thymine dimer repair severely compromised -7 variations (A-G): each complementation group represents a mutation in an individual NER protein (all first 3 steps- recognition, endonuclease nicking, helicase/exonuclease removing damaged DNA) -treatment: protect from UV (limited effectivemess) |
