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8/18 DNA Mutations
Crawford Theme1
35
Biology
Graduate
08/28/2011

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Term
Etopoicide
Definition
- Prevents topo2 from untangling mitotic DNA strands; stops cell division
Term
DNA fidelity occurs because of:
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
Term
Mismatch Repair
Definition
- Scanning protein picks up distortion by checking against the parent strand which is marked by methylation prokaryotes and some unknown method in eukaryotes
Term
Mutation
Definition
a stable change in DNA structure. Mutations can be phenotypically silent or expressed
Term
Base substitution
Definition
Transition; purine to purine or pyr to pyr
Transversion; pur to pyr or vice versa
Term
Frame Shift
Definition
insertion or deletion of bases(s) that changes the normal codon reading frame.
2) Acridine Orange, Ethid Bromide, Benzopyrene
Term
Effects of mutation
Definition
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
Term
Point mutation
Definition
- change in a single base pair in a gene. Usually another term for a base
substitution.
Term
Silent mutation
Definition
- 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
Term
Missense Mutation
Definition
- base change leading to the incorporation of a different amino acid in the
protein. The best known example is sickle cell anemia
Term
Nonsense mutation
Definition
Creation of a stop codon instead
Term
Frame shift mutation
Definition
- insertion or deletion of base(s).
Term
intercalating agents
Definition
- which are aromatic organic compounds that insert between base pairs in double-stranded DNA.
Term
Mutagen
Definition
- an agent that can cause a mutation. The major mutagens are chemicals and radiation
Term
Damage
Definition
- 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
Term
Oncogene
Definition
Genes commonly mutated or aberrantly expressed in transformed cells. They are
usually identified by three-letter acronyms
Term

Tumor Suppressor Gene

-2 examples

Definition
Gene whose protein product is required to keep cell proliferation under control. Examples include p53 and Rb.
Term
Alkylating Agents
Definition
Remove a base, modify base
Term
UV
Definition
-Causes Dimerization; pyrmidine
-Usually UVB
Term
Intrastrand Adduct
Definition
Bond between adjacent bases
Term
Strand break
Definition
X-rays
Term
Modified Base
Definition
Alkylating Agent
Term
Chemical deamination
Definition
- Nitric Acid deaminates Cytosine to Uracil and Adenine to Hypoxanthine
Term
Alkylation
Definition
- Methylates N in Guanine to make 7-methyl guanine
- Especially bad because it can cause cross linking and breaks
Term
UV radiation
Definition
- Causes forming of dimers in adjacent bases; pyrmidines
Term
Ionizing radiation
Definition
- 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
Term
Spontaneous Mutation
Definition
- Most common base damage esp depurination
- Depurination = spontanous A/G loss
- Deamination from cytosine to uracil
Term
Mitochondria
Definition
Very susceptible to mutation because
1) Naked DNA; little or no protein associated for protection
2) Electron TC creates oxidants
3) Weaker repair systems
Term
Liebers Neuropathy
Definition
Mitochondirian DNA mutation, first pathology related to mitDNA
Term
Mutation Detection
Definition
- Animals in cancer study
- Needed lots of animals
Term
Ames test
Definition
- 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)
Term
Cancers
Definition
Altered expression of oncogenes and tum sup genes
Term
Thalassemias
Definition
Defect in co-ord synth of A and B globin; can result from any of the mutations
Term
Mitochondial Defects
Definition
Lebers, Myoclonic epilepsy, AD/PD (?), late onset diabetes
Term
Clinical Mutagens
Definition
Radiotherapy; can have secondary tumors as a result creates oxidants etc etc
Chemicals; cisplatin, bleomycin, mitomycin etc
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