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The ability to utilize UV light to cross-link bases in double-stranded and triple-stranded DNA, or cross-link bases in oligonucleotides with other types of molecules (such as proteins), is often a necessary for successful performance of structural studies, for example the probing of nucleic acid secondary structure, or the structure of protein-nucleic acid complexes. Cross-linker modifications generally fall into two categories, nucleic acid intercalators (for example, psoralen) and halogenated bases (for example, 5-Br-dC). Incorporation of a nucleic acid intercalator into an oligo permits site-specific targeting of the cross-link into double-stranded and triple-stranded DNA. Incorporation of a modified base, capable of forming cross-links, into an oligonucleotide is often the method of choice when an intra-strand cross-link is needed, or a direct cross-link to a protein or other molecule is desired.
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