Mutation and Cancer:

1) How can recombination within a gene create new alleles? Why is this a probable way that new alleles form, in the context of the functional relationship between exons and the proteins they encode?

2) Why are base insertions/deletions apt to be more deleterious than a substitution?

3) What's the difference between a spontaneous and induced mutation?

4) List four different effects that a substitution mutation can have, including two ways that a change in DNA can be 'silent'.

5) Bases can exist as tautomers - structural isomers that shift between a keto (=O) and enol (-OH with a doubly bound neighboring carbon) forms. Exaplin how a tautomeric shift can cause a base-pair substitution.

6) What is depurination, and how does DNA polymerase respond to this change in the DNA template?

7) Why is oxidation such a common and pervasive risk to DNA? Show how oxidation of a singleton guanine base causes a base pair substitution.

8) How does replication slippage cause insertions and deletions?

9) How does the number of trinucleotide repeat sequences affect the expression of Huntington's Chorea and frgile-X syndrome? How does the mechanism of this action differ between these two conditions?

10) What is 'genetic anticipation', and how is it caused by replication slippage?

11) Why are sequences with micro- or minisatellites used for DNA fingerprinting? Include the structural differences between indivudals in these regions, and the use of restriction enzymes and gel elecrophoresis to resolve these differences.

12) Bacteria have two types of transposons, IS and Tn. What are the characteristics of each?

13) List three ways that transposons can affect gene function.

14) What beneficial effect do transposons have in Drosophila?

15) What are p-elements, how is their jumping regulated?

16) How can transposons affect recombination?

17) A base analog is a chemical that can bind in place of a nitrogenous base. But why is that a problem? It 5-bromouracil binds in place of thymine, for instance, and if it still binds to adenine, how can this cause a mutation?

18) In the Ames test, what do we know about cells from a stock that was his- that can now grow on minimal medium? If this stock has not been exposed to any putative mutagen, what does the number of these colonies growing on minimal medium represent? So, if we expose replicate samples to a chemical and get more colonies growing on minimal medium, what can we infer about the effect of the chemical? Why might we include liver enzymes?

19) Repair enzymes 'proofread' the DNA during the G1 and G2 periods of the cell cycle. They recognize and correct 'mismatched' base pairs, like A=G. How is the incorrect base identified?

20) UV radiation causes thymidine dimerization. How is this repaired?

21) More intense radiation can cause 'double-stranded breaks' in DNA. Curiously, the 'blunt ends' of the pieces are not just ligated back together. Instead, a rather complicated process is performed of using the identical sister chromatid (in G2, or the homolog in G1) to repair the lesion. What is the benefit of using this method, compared to just ligating blunt DNA ends together?

22) What genetic evidence exists that most tumors have proliferated from a single cell?

23) What are CDK's, how do they exert their effect, and what stimulates their activity? What is E2F and what does it do? Describe the pathway that activates E2F.

24) How do c-myc and p53 proteins influence the CDK-4 pathway?

25) What do the ras family of proteins do? How do they do it?

26) What are the relationships between proto-oncogenes and oncogenes?

27) describe two ways that viruses can cause cancer.