Chapter 14, Problem 24PDQ

Electrophilic oxidants are known to create the modified base named 7,8-dihydro-8-oxoguanine (oxoG) in DNA. Whereas guanine base-pairs with cytosine, oxoG base-pairs with either cytosine or adenine.

(a) What are the sources of reactive oxidants within cells that cause this type of base alteration?

(b) Drawing on your knowledge of nucleotide chemistry, draw the structure of oxoG, and, below it, draw guanine. Opposite guanine, draw cytosine, including the hydrogen bonds that allow these two molecules to base-pair. Does the structure of oxoG, in contrast to guanine, provide any hint as to why it base- pairs with adenine?

(c) Assume that an unrepaired oxoG lesion is present in the helix of DNA opposite cytosine. Predict the type of mutation that will occur following several rounds of replication.

(d) Which DNA repair mechanisms might work to counteract an oxoG lesion? Which of these is likely to be most effective?