Term
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Definition
the mutation changes one codon for an amino acid into another codon for that same amino acid ; silent mutation
- this can happen because the genetic code is degenerate
-base pair change = same amino acid |
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Term
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Definition
– the codon for one amino acid is changed into a codon for another amino acid ; non synonymous mutation
2 types: conservative and nonconservative |
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Term
| conservative substitution |
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Definition
replaces one amino acid with a chemically similar amino acid (less likely to alter the proteins function severely)
-probability of having effect on phenotype is small |
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Term
| nonconservative substitution |
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Definition
the amino acid is replaced by a chemically different amino acid (more likely to produce a severe change in protein structure and function)
-much more likely to have a significant effect on phenotype |
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Term
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Definition
-codon for one amino acid is changed into a translation-termination (stop) codon – leads to the premature termination of translation
-have considerable effect on protein function – the closer a nonsense mutation is to the 3’ end of the open reading frame, the more likely the protein will possess biological activity → many produce completely inactive protein products |
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Term
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Definition
-when a deletion or insertion occurs of a single base pair that changes the reading frame for the remainder of the translation process, from the site of the base-pair mutation to the next stop codon in the new reading frame
-out of frame, making a different set of amino acids
-typically result in complete loss of normal protein structure and function
-due to insertions or deletions |
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Term
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Definition
-deletion or insertion of a base *short regions of DNA*
- if this occurs in a protein encoding region (particularly one base pair) → dramatic change, changing the frame
-Where does this happen? repetitive sequences of DNA during replication (highest portion occurs here) - most caused by slipped mispairings during DNA replication |
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Term
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Definition
-these can be generated by different processes - replication errors and spontaneous lesions generate most spontaneous base substitutions - replication errors can also cause deletions that lead to frameshift mutations
types: depurination, deamination, and oxygen radical damage |
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Term
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Definition
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Term
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Definition
Unmethylated: C -> U in DNA
Methylated: C -> T |
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Term
| trinucleotide repeat mutations |
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Definition
| arise through the expansion of the number of copies of a three-base pair sequence normally present in several copies, often within the coding region of the gene; a common mechanism responsible for a number of genetic diseases is the expansion of a three-base-pair repeat i.e. fragile X syndrome |
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Term
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Definition
-an example where replication slippage in a gene can give rise to a mutation
-most common form of inherited mental impairment; results in changed in the number of (CGG) repeats in the region of the FMR-1 gene
3 States:
Normal – 5-60 repeats
Pre mut – 60-200 repeats → phenotype normal but @ risk
Mutation – 200–1300: Disease → too large, methylated
-the more repeats you have -> the higher amount your children will have; would rather have low end: mutations build up as generations go on
-Will lose people who have this large chromosome because they will die/not have many children - mutant chromosomes become lost in the population |
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Definition
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Term
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Definition
-covalently change bases in some way, damaging the bases:
-replace base in the DNA
-alter a base that it specifically mispairs with another base
-damage a base so that it can no longer pair with any base under normal conditions
i.e. gasoline vapor, contents in cigarettes, carcinogens |
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Definition
-causes the most damage: messes up replication, RNA synthesis, etc.
-damage to the bases
-causes cyclobutyl ring between 2 T's
-causes photodimer |
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Term
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Definition
| -repairs photodimer caused by UV light-an enzyme that binds to the photodimer and splits it to regenerate the original bases -> repair mechanism called photo reactivation because the enzyme requires light to function |
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Term
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Definition
| a location in DNA that has neither a purine nor a pyrimidine base, either spontaneously or due to DNA damage |
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Term
| homology dependent repair systems |
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Definition
| depend on complementarity (homology) of the template strand to the strand being repaired |
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Term
| base-excision repair (BER) |
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Definition
most important mechanism used to remove incorrect or damaged bases (after DNA proofreading by DNA polymerase)
-type of homologous repair
main target: nonbulky damage to bases
-damage recognized by one of the several enzymes called DNA glycosylases that cleave the base-sugar bonds, releasing the incorrect base
repair: the removal of the site that now lacks a base and the insertion of the correct base as guided by the complementary base in the undamaged strand
process:
-glycosylases seek damaged bases
-cut DNA & clear small section around damage (with endonuclease)
-polymerase and ligase fix it using sister strand |
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Term
| nucleotide excision repair (NER) |
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Definition
recognizes and corrects DNA lesions due to largely UV damage, and in doing so, relieves stalled replication forks and transcription complexes (bulky/consecutive)
-done when base excision won't work
4 phases:
•recognition of damaged bases
•assembly of a multiprotein complex at this site
•cutting of the damaged strand several nucleotides upstream and downstream of the damage site and removal of the nucleotides between the cuts
•use of the undamaged strand as a template for DNA polymerase followed by strand ligation
*this system corrects errors in replication that are not corrected by proofreading function of the replicative DNA polymerase – repair is restricted to the newly synthesized strand which is recognized by the repair machinery in prokaryotes because it lacks a methylation marker |
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Term
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Definition
– corrects the remaining replication error – reduces the error rate to less than 10^-9 by recognizing and repairing mismatched bases and small loops caused by indels in the course of replication (loss of mismatch repair is a big problem)
-once mismatched bases are taken away -> DNA polymerase comes by again and makes new strand again to correct mismatch |
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Term
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Definition
| this enzyme follows behind DNA polymerase which then recognizes the mismatch initiating repair |
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Term
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Definition
-recognizes parent strand by epigenetic marks on the DNA (in E.coli): old strand is methylated so that the un-methylated strand, the new DNA is obvious
-determines which base in the mismatch is the incorrect one |
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Term
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Definition
| -comes in and cuts out new strand that was just made by DNA polymerase |
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Term
| Error prone repair pathways |
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Definition
-evolved to prevent the occurrence of more serious outcomes such as cell death or cancer
-If you are not replicating DNA correctly/in a timely manner → signal sent out so the cell commits suicide because no repair mechanism comes around unless translesion synthesis happens |
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Term
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Definition
*mistakes are better than DNA breaks*
-Necessary if nucleotide excision repair is busy correcting other damages (last-minute method to try to avoid DNA damage)
-Bypass polymerases comes in to get you past the damage and then the DNA can be replicated (hope is that next time you replicate the DNA, the damage can be corrected)
-Bypass polymerases are recruited to replication forks that have stalled because of damage in the template strand |
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Term
| non homologous end joining (NHEJ) |
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Definition
-repairs double-stranded DNA break
-error-prone pathway that repairs double-strand breaks in higher eukaryotes by ligating the free ends back together |
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Term
| synthesis dependent strand annealing (SDSA) |
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Definition
-error-free mechanism that repairs double-stranded breaks in dividing cells in which a sister chromatid is available to serve as template for repair synthesis
-used if meiotic recombination goes wrong (cross-over) |
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Term
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Definition
oncogene: mutated - cell division doesn't stop (always turned on) - promotes cell-cycle progression and inhibits apoptosis
proto-oncogene: not mutated - turn on or increase rate of cell division - cells grow and divide when these genes are active |
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Term
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Definition
-turn off or decrease the rate of cell division, repair DNA mistakes, play a role in apoptosis (suppresses tumors)
-mutated: won’t have the ability to stop a cell from diving in an uncontrolled manner (always turned off) |
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Definition
| when a cell commits suicide |
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Term
| another explanation for alternative splicing |
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Definition
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Term
| What's the only molecule we care to repair? |
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Definition
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Term
| When is Nucleotide Excision Repair done? |
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Definition
•RNA polymerase – Transcription-coupled nucleotide-excision repair - Repairs transcribed regions of DNA
•DNA polymerase – global genomic repair
Corrects lesions anywhere in the genome and is activated by stalled replication forks |
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Term
| double-stranded DNA break |
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Definition
-if left unrepaired, can cause a variety of chromosomal aberrations resulting in cell death or a precancerous state
-can arise spontaneously or be induced by ionizing radiation |
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Term
| Difference between base-excision repair and nucleotide-excision repair |
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Definition
| there is an enzyme always scanning to find a damaged base for base-excision repair, while for nucleotide-excision repair a transcription block initiates this repair (triggered by RNA polymerase) |
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Term
| SDSA can happen alone or in meiosis |
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Definition
Meiosis: synthesis is occurring between two homologs and the break is generated by an enzyme making the cut - caused deliberately ~ you also get recombination
SDSA: occurring between chromatids, DNA break is caused randomly (i.e. UV radiation, etc.) |
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