ADL Lecture 6: 12.4-12.8 Flashcards
TYPES OF MUTATION AND DNA REPAIR, II
Tautomers
DNA nucleotide bases are organic chemical structures that can convert to an alternative structure. Have slight differences in bonding/ placement of hydrogens.
Tautomeric shifts
Leads to base-pair mismatches/ incorporation of incorrect bases during replication. Most common form of replication error.
Base-pair substitution mutation
replacement of one single nucleotide base pair by another
Transition mutation
replace one pyrimidine base with the other or one purine base with the other. (4 possible mutations)
Transversion mutation
replace a pyrimidine with a purine or vice versa. (8 possible mutations)
Ratio between transition : transversion
If bases were equally frequent–
Among spontaneous base substitutions–
1: 2
2: 1
Dupurination
loss of a purine from a nucleotide by breaking the covalent bond linking the nucleotide base to the sugar.
Apurinic site
an unrepaired lesion at a site that as lost its purine nucleotide base.
How does DNA polymerase compensate when a strand loses a purine nucleotide?
putting an adenine (A) into the site during replication. (Note: the template strand will produce a wild type duplex while the coding strand will produce the mutant daughter duplex.)
Deamination
loss of an amino group (NH2) from nucleotide. When C is deaminated, it’s converted into U. DNA removes U and replaces it with C… restoring wild-type sequence.
When methylated C is deaminated, it’s replaced with T. This can lead to production of wild-type or mutant type sequencing.
Mutations are ____ with respect to position in a gene or genome.
nonrandom
Mutation Hot Spots
certain dna sequences are more likely to undergo mutation that others. i.e. sites of C methylation due to the way deaminated bases are repaired.
Induced mutation
produced by interactions between DNA and physical, chemical or biological agents that generate mutations.
Mutagens
Agents that cause DNA damage leading to mutations
Chemical mutagens can be classified by their modes of action on DNA as: (6)
nucleotide base analogs deaminating agents alkylating gents oxidizing agents hydroxylating agents intercalating agents
Mutagenic event/Type of Agent:
- Transition mutation/ ___
- Transversion mutation/ ____
- Frameshift/ ___
- Base analog / alkylating agent / hydroxylating agent / deaminating agent
- oxidative agent
- intercalating agent
What types of radiation have higher energy than UV light?
x-rays/ radioactive materials
What kind of damage does radiation have on DNA?
single/double stranded breaks in DNA (note the difference between this and chemical mutagens) Thesis breaks can block DNA replication
Ames test
A genetic test for mutations in bacteria that is widely used for detecting of chemical mutagens
Carcinogens
agents that cause cancer (are also mutagens) and mutagenicity provides initial screening for potential hazardous agents.
Cancer typically requires ___ to ___ ___ genes. An elecated mutation rates makes those hits far more likely to occur in the same cell.
two-hits; tumor suppressor
DNA damage signaling systems
biochemical mechanisms recognize presence of DNA lesions and initiate repair response consist of a tightly regulated genetic process. (throughout cell cycle)
What is the role of the p53 repair pathway?
How does this pathway control cell responses to mutation?
-p53 inactive in large majority of tumors
- Pause in cell cycle at the G1-S transition to allow time for repair or
- Direct cell to undergo programmed cell death
Why is Li-Fraumeni considered autosomal dominant when mutations in p53 are inherited in single copy and they are strict loss of function mutations?
Because it takes “two-hits” to actually develop a cancer? Therefore, homozygous mutant p53 is not enough to cause cancer…other mutations must be present as well.
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