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DNA lesion poses a triple threat A common type of DNA damage may give rise to proteins lacking a single amino acid, examples of which have been implicated in cancer and other diseases. A variety of DNA-damaging agents, including -radiation and antitumor agents such as the enediynes and bleomycin, create abasic sites (shown) that are oxidized at the 4´-position of the deoxyribose ring (red). Marc M. Greenberg and coworkers at Johns Hopkins University show that when DNA containing such an abasic site undergoes replication in bacteria, the lesion causes the deletion of three consecutive nucleotides in the DNA [Biochemistry, 43, 13621 (2004)]. Three-nucleotide deletions may be unusually detrimental to cells because they can lead to the production of proteins that lack a single amino acid, Greenberg points out. One- or even two-nucleotide deletions--which are far more common--give rise to grossly altered proteins that the cell quickly destroys. But the deletion of a single amino acid, he adds, "is a far more subtle alteration" that isn't readily recognized and fixed by the cell |
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