1. How is the fidelity of DNA replication affected by the fact that DNA polymerase adds nucleotides only to a primer strand that is hydrogen-bonded to the template?

This property of DNA polymerases is necessary for proofreading because it enables the polymerase to recognize and excise mismatched bases that are not hydrogen-bonded to the template strand.

2. Would you expect the RNA fragments synthesized by primase to be accurate copies of the template DNA? How does this affect the overall accuracy of DNA replication?

Primase, like other RNA polymerases, is not capable of proofreading, so errors occur at a comparatively high frequency in RNA primers. However, since the primers are later removed, the overall fidelity of replication is not compromised.

3. Patients with xeroderma pigmentosum suffer an extremely high incidence of skin cancer but have not been found to have correspondingly high incidences of cancers of internal organs (e.g., colon cancer). What might this suggest about the kinds of DNA damage responsible for most internal cancers?

The high frequency of skin cancer results from DNA damage induced by solar UV irradiation, which is subject to repair by the nucleotide-excision repair system. The lack of elevated incidence of other cancers may suggest that similar types of damage are not frequent in internal organs and that most cancers of these organs result from other types of mutations (e.g., the incorporation of mismatched bases during DNA replication).

4. RecA mutants of E. coli are sensitive to UV irradiation in addition to being recombination-deficient. Why?

RecA mutants are sensitive to UV irradiation because they are deficient in recombinational repair of DNA damage.

5. What phenotype would you predict for a mutant mouse lacking one of the genes required for site-specific recombination in lymphocytes?

The mouse would be immunodeficient, lacking both B and T lymphocytes, as a result of being unable to rearrange its immunoglobulin and T cell receptor genes.

6. Many of the drugs in clinical use and under evaluation for the treatment of AIDS are inhibitors of the HIV reverse transcriptase. What reverse transcriptases in human cells might also be inhibited by these drugs? What would be the consequences of inhibiting these enzymes?

The cellular reverse transcriptases that might be affected by these drugs include telomerase and the reverse transcriptases encoded by LINE sequences. Inhibition of the LINE reverse transcriptases would not be toxic to the cell, but inhibition of telomerase might interfere with the replication of chromosome ends.