ADL Lecture 6: 12.4-12.8

Question 1

Tautomers

Answer 1

DNA nucleotide bases are organic chemical structures that can convert to an alternative structure. Have slight differences in bonding/ placement of hydrogens.

Question 2

Tautomeric shifts

Answer 2

Leads to base-pair mismatches/ incorporation of incorrect bases during replication. Most common form of replication error.

Question 3

Base-pair substitution mutation

Answer 3

replacement of one single nucleotide base pair by another

Question 4

Transition mutation

Answer 4

replace one pyrimidine base with the other or one purine base with the other. (4 possible mutations)

Question 5

Transversion mutation

Answer 5

replace a pyrimidine with a purine or vice versa. (8 possible mutations)

Question 6

Ratio between transition : transversion
If bases were equally frequent–
Among spontaneous base substitutions–

Answer 6

1: 2
2: 1

Question 7

Dupurination

Answer 7

loss of a purine from a nucleotide by breaking the covalent bond linking the nucleotide base to the sugar.

Question 8

Apurinic site

Answer 8

an unrepaired lesion at a site that as lost its purine nucleotide base.

Question 9

How does DNA polymerase compensate when a strand loses a purine nucleotide?

Answer 9

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.)

Question 10

Deamination

Answer 10

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.

Question 11

Mutations are ____ with respect to position in a gene or genome.

Answer 11

nonrandom

Question 12

Mutation Hot Spots

Answer 12

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.

Question 13

Induced mutation

Answer 13

produced by interactions between DNA and physical, chemical or biological agents that generate mutations.

Question 14

Mutagens

Answer 14

Agents that cause DNA damage leading to mutations

Question 15

Chemical mutagens can be classified by their modes of action on DNA as: (6)

Answer 15

nucleotide base analogs
deaminating agents
alkylating gents
oxidizing agents
hydroxylating agents 
intercalating agents

Question 16

Mutagenic event/Type of Agent:

1. Transition mutation/ ___
2. Transversion mutation/ ____
3. Frameshift/ ___

Answer 16

1. Base analog / alkylating agent / hydroxylating agent / deaminating agent
2. oxidative agent
3. intercalating agent

Question 17

What types of radiation have higher energy than UV light?

Answer 17

x-rays/ radioactive materials

Question 18

What kind of damage does radiation have on DNA?

Answer 18

single/double stranded breaks in DNA (note the difference between this and chemical mutagens) Thesis breaks can block DNA replication

Question 19

Ames test

Answer 19

A genetic test for mutations in bacteria that is widely used for detecting of chemical mutagens

Question 20

Carcinogens

Answer 20

agents that cause cancer (are also mutagens) and mutagenicity provides initial screening for potential hazardous agents.

Question 21

Cancer typically requires ___ to ___ ___ genes. An elecated mutation rates makes those hits far more likely to occur in the same cell.

Answer 21

two-hits; tumor suppressor

Question 22

DNA damage signaling systems

Answer 22

biochemical mechanisms recognize presence of DNA lesions and initiate repair response consist of a tightly regulated genetic process. (throughout cell cycle)

Question 23

What is the role of the p53 repair pathway?

How does this pathway control cell responses to mutation?

Answer 23

-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

Question 24

Why is Li-Fraumeni considered autosomal dominant when mutations in p53 are inherited in single copy and they are strict loss of function mutations?

Answer 24

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.
?

Question 25

Why was the observation that Li-Fraumeni affecters suffer from a high rate and early incidence of all forms of cancer and not one particular type of cancer so important?

Answer 25

Case study shows how speciifc types of cancer develop on specific genes/tissues/cells depending on type of mutation. There are also speific repair mechanisms that may increase susceptibility to cancer or have no effect in repairing mutation.

Question 26

How does understanding Li-Fraumeni syndrome help us see cancer as a two-hit process?

Answer 26

If a cell/tissue/gene is mutated, a repair mechanism may be able to inhibit further transcription (progam cell death) or “fix” the cell/gene/tissue and carry on throughout the cell cycle normally. If a damaged (mutated) cell proceeds in the cell cycle, rapid cell growth occurs.

Question 27

Meiotic recombination is a genetically controlled process initiated by ___

Answer 27

enzymes that induce double stranded DNA breaks

Question 28

How does a double strand break lead to a Holliday Junction? What is a Holliday junction?

Answer 28

HJ is a DNA structure that forms during meiotic recombination in which single strands are crossed over between nonsister chromatids of homologous chromosomes.
A DS break leads to HJ at the deteroduplex region-where strand invasion creates a D loop between nonsister chromatids of homologous chromosomes.

Question 29

Holliday Junction Resolution:
Occurs when in the cell cycle?
What are the two patterns that can occur?

Answer 29

Must be resolved before metaphase I to allow proper separation.
Same sense/ opposite sense resolution

Question 30

Same sense resolution

Answer 30

produces offset heteroduplex regions but no recombination of flanking genes. This resolution occurs infrequently.

Question 31

Opposite sense resolution

Answer 31

Very common. Generates recombination of flanking genes and creates offset heteroduplex regions. (resulting chromosomes are recombinant and lead to recombinant progeny)

Question 32

Gene conversion

Answer 32

Repair of mismatched DNA nucleotides in heteroduplex DNA that forms during meiotic recombination. One allele is switched for another allele already in the genotype.