Ionizing radiation and radiomimetic drugs such as bleomycin, calichieamycin, 
neocarzinostatin chromophore, and other synthetic agents can produce both single 
and double strand breaks in DNA. The ability to study the structure-activity 
relationships of single and double-strand break repair, lethality, and 
mutagenesis in vivo is complicated by the numerous types and sites of DNA 
cleavage products that can be induced by such agents. The ability to "cage" such 
breaks in DNA might help to further such studies and additionally afford a 
mechanism for activating and deactivating nucleic acid based drugs and probes. 
The major type of single strand break induced by ionizing radiation is a 3'- and 
5'-phosphate terminated single nucleotide gap. Previously, a caged strand break 
of this type had been developed that was designed to produce the 5'-phosphate 
directly upon irradiation with 366 nm light, and the 3'-phosphate by a 
subsequent beta-elimination reaction [Ordoukhanian, P., and Taylor, J.-S. (1995) 
J. Am. Chem. Soc. 117, 9570]. Unfortunately, the release of the 3'-phosphate 
group was quite slow at pH 7. To circumvent this problem, a second caged strand 
break has been developed that produces the 3'-phosphate directly upon 
irradiation, and the 5'-phosphate by a subsequent beta-elimination reaction. 
When this caged strand break was used in tandem with the previous caged strand 
break, 5'- and 3'-phosphate terminated gaps could be directly produced by 
irradiation with 366 nm light. These caged single strand breaks were also 
incorporated in tandem into hairpin substrates to demonstrate that they could be 
used to cage double strand breaks. These caged single strand breaks should be 
generally useful for generating site-specific DNA single and double strand 
breaks and gaps, using wavelengths and doses of light that are nondetrimental to 
biological systems. Because the position of the single strand break can be 
varied, it should now be possible to examine the effect of the sequence context 
and cleavage pattern of single and double strand breaks on the lethality and 
mutagenicity of this important class of DNA damage.