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- Prevents topo2 from untangling mitotic DNA strands; stops cell division |
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DNA fidelity occurs because of: |
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Definition
1) High synthetic fidelity of DNA Pol 2) Proof reading 3' to 5' exonuclease 3) Mismatch repair
- Fidelity itself accounts for 1/100,000 mistakes but proof-reading bumps it to 1 billion |
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- Scanning protein picks up distortion by checking against the parent strand which is marked by methylation prokaryotes and some unknown method in eukaryotes |
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a stable change in DNA structure. Mutations can be phenotypically silent or expressed |
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Transition; purine to purine or pyr to pyr Transversion; pur to pyr or vice versa |
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insertion or deletion of bases(s) that changes the normal codon reading frame. 2) Acridine Orange, Ethid Bromide, Benzopyrene |
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1) Deleterious; usually by changing a crucial protein 2) Cell death (and loss of the mutation) 3) Silent; in some non essential area 4) Beneficial; and may replace the original through selection |
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- change in a single base pair in a gene. Usually another term for a base substitution. |
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- base change leading to the incorporation of the same amino acid in the protein. This base change often occurs in the third position of a codon |
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- base change leading to the incorporation of a different amino acid in the protein. The best known example is sickle cell anemia |
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Creation of a stop codon instead |
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- insertion or deletion of base(s). |
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- which are aromatic organic compounds that insert between base pairs in double-stranded DNA. |
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- an agent that can cause a mutation. The major mutagens are chemicals and radiation |
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- base modifications, nucleotide deletions and insertions, crosslinking of DNA strands, and breakage of the phosphodiester backbone. Most damage is repaired. Only damage that escapes repair becomes a mutation |
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Genes commonly mutated or aberrantly expressed in transformed cells. They are usually identified by three-letter acronyms |
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Tumor Suppressor Gene
-2 examples |
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Definition
Gene whose protein product is required to keep cell proliferation under control. Examples include p53 and Rb. |
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Remove a base, modify base |
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-Causes Dimerization; pyrmidine -Usually UVB |
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Bond between adjacent bases |
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- Nitric Acid deaminates Cytosine to Uracil and Adenine to Hypoxanthine |
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Definition
- Methylates N in Guanine to make 7-methyl guanine - Especially bad because it can cause cross linking and breaks |
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- Causes forming of dimers in adjacent bases; pyrmidines |
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- Direct; photon reduces DNA causing breaks - Indirect; creates hydroxyl radical which acts as strong damaging oxidant - Increases incidince of minor tautomer formation; improper base pairing |
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- Most common base damage esp depurination - Depurination = spontanous A/G loss - Deamination from cytosine to uracil |
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Very susceptible to mutation because 1) Naked DNA; little or no protein associated for protection 2) Electron TC creates oxidants 3) Weaker repair systems |
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Mitochondirian DNA mutation, first pathology related to mitDNA |
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- Animals in cancer study - Needed lots of animals |
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- Mutagen added to bacteria along with rat liver extract and mutation rate of bacteria measured. - Most mutagens in bacteria are mutagens in humans - Mutagen = carcinogen (assumed) |
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Altered expression of oncogenes and tum sup genes |
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Defect in co-ord synth of A and B globin; can result from any of the mutations |
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Lebers, Myoclonic epilepsy, AD/PD (?), late onset diabetes |
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Radiotherapy; can have secondary tumors as a result creates oxidants etc etc Chemicals; cisplatin, bleomycin, mitomycin etc |
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