Term
| DNA damage to resting DNA |
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Definition
-As a result of unavoidable environmental influences.
1)We will consider several such types of damage—all of which generate pre-mutagenic lesions that can become
permanent at the next round of DNA replication: (a) the covalent cross-linking of adjacent pyrimidine nucleotides, (b) the transformation of cytosine into ‘thymine’, and (c)
the loss of a purine or pyrimidine base by a nucleotide. |
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Term
| Covalent Cross-linking of Adjacent Pyrimidine Nucleotides |
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Definition
1)UV light causes Pyrimidine dimers.
2)Doesn't change H-bonding but changes orientation of nitrogenous bases such that DNA polymerase either stalls or adds an incorrect base to the information strand. |
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Term
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Definition
-Thymine Dimers
1)Takes advantage of the fact that there is a complementary DNA template strand.
2)A specialized repair endonuclease recognises the distortion in the DNA caused by the thymine dimer and then breaks two phosphodiester bonds in the damaged strand, on either side of the lesion.
3)DNA helicase moves in and excises the polynucleotide chain.
4)DNA repair polymerase (poly III) fills in the missing nucleotides and DNA ligase repairs the nicks if necessary. |
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Term
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Definition
Inherited human disease
Presenting as a hypersensitivity to sunlight and a serious tendency to develop skin cancer. Individuals with this illness cannot manufacture one of the enzymes involved in the repair of Pyrimidine Dimers. |
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Term
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Definition
1)Cytosine in inherently unstable (labile). It is subject to a nucleophilic attack by an OH— ion derived from the dissociation of a water molecule. The resulting loss of the amino group will make it resemble U in the enol form and will no longer allow it to form triple H bonding to G.
2)The new "U", is like RNA except it lacks a hydroxyl group at the 2' sugar residue position. It will tautomerize to its keto form and H-bond to A. |
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Term
| Repairing DNA with a Deaminated Cytosine |
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Definition
1) An enzyme (Uracil DNA Glycosylase) recognises the base that lacks the expected methyl group (deaminated cytosine, or U) and hydrolyses the glycosidic linkage that holds the base to the deoxyribose sugar.
2)The nucleotide with the missing base is recognised by an enzyme (Apyrimidinic Nuclease, or AP nuclease), which then cleaves the sugar-phosphate backbone.
3)DNA Polymerase b adds the missing nucleotide and DNA Ligase seals the nick. |
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Term
| Damage to a Resting DNA Double Helix |
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Definition
1)A random nucleotide is going to lose its purine or pyrimidine base.
2)The nitrogenous base will need to be replaced to minimize a chance of mutation during DNA replication AND/OR prevent the DNA template from buckling, resulting in a deletion mutation. |
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Term
| Errors during DNA replication |
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Definition
An important method for generating mutations that add or delete base pairs from DNA.
1)Mutations that add or delete base pairs can arise during replication from DNA strand slippage. Result is longer DNA information strand (Two extra CAGs--polyglutamine--e.g.: Huntington Disease).
2)DNA mismatch repair-similar to excision repair, remember it's also ATP-driven (helicase). *Q is, how does DNA nuclease recognize which strand has the BP mutation? The strand that has been around longer would be methylated.* |
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Term
| Components of Mismatch Repair Enzyme (2) |
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Definition
1)MutS
a)Consists of two subunits.
b)One of the subunits of MutS is MSH2, which is frequently defective in hereditary colon cancer, commonly abbreviated as HNPCC (hereditary non-polyposis cancer of the colon)
2)MutL
a)Consists of two subunits.
b)One of the subunits of MutL is MLH1, which is frequently defective in HNPCC.
[BRCA2 and RAD51 stimulate strand invasion. BRCA2 is one of the genes mutated in familial breast cancer.] |
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Term
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Definition
1)Backup template strand
2)Backup chromosome
3)Final backup: Cell cycle checkpoints
4)If all fails, you have cancer.
*Genetic disease termed Ataxia-telangiectasia caused by a defective in a Checkpoint protein. This disease includes a predisposition to cancer.* |
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Term
| Homologus recombination repair |
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Definition
| Repair by Strand Invasion when one chromosome is simulatenously nicked at the same time. |
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Term
| Recombination Functions (6) |
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Definition
1)Meiosis
2)Gene Conversion
3)Generation of Antibodies
4)Trinucleotide repeat expansions
5)Gene deletion
6)Viral genome integration |
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Term
| Diversity mechanisms tally for meiosis. |
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Definition
1)Independent assortment of homologs with respect to each other: Some gametes get the paternal, and some gametes get the maternal version.
2)Essentially random recombination between maternal and paternal homologs
3)Essentially random gene conversion possibilities at the recombination junctures.
4)Unequal crossing over. |
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Term
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Definition
| Nick in dSDNA in one chromosome and mutation in other chromosome, result of strand invasion are mutant strands. |
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Term
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Definition
| Result of recombination and selective exon splicing. |
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Term
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Definition
| In Thalesmeia. Can be lost through recombination. |
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Term
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Definition
| Recombination Event, lysogenic until trigger. Transposon "jumping gene"--basically transfers DNA from strand 1 by being completely excised from strand 1 by recombination and recombined with strand 2. |
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Term
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Definition
DNA recombination leads to genetic diversity. Depending on whether or not mismatch repair enzymes are present during recombination, the Holliday junction formed from 2 homologous strands will either result in a cross-over product or a gene conversion product (non-crossover). The latter is due to the repair enzymes completely excising the mismatched "different" allele segment (heteroduplex). Also, sometimes there is uneven DNA recombination where they recombine at unequal segments of the chromosome. This can lead to gene duplication or disjunction which may further lead to disease (such as Thallasemia).
Gene duplication can also occur by excising out DNA through a recombination event into a circular strand which can recombine again with one of the original strands. |
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