Bent DNAs Help Probe DNA-Protein Binding

Many DNA-protein interactions involve structural distortions of the DNA helix. A new class of artificial DNAs, called "modular bent DNAs," could help systematically assess the role that DNA bending plays in these interactions, according to a recent study (J. Am. Chem. Soc., DOI: 10.1021/ja071335k).

Akira Matsuda, Satoshi Ichikawa, Shunpei Murata, and coworkers at Hokkaido University, Sapporo, Japan, create their bent DNA oligonucleotides by adding cyclic 2'-deoxyuridylate dimers connected by alkylene linkers. Oligonucleotides with shorter alkylene "clasps" have larger bending angles and are thermally less stable.

The researchers tested the bent DNAs by binding them to HMGB1, a protein known to interact with DNA-cisplatin adducts, which are themselves bent DNAs. The binding affinity of the bent DNA decreases as the linker length increases, and the oligonucleotide with a propylene bridge doesn't form a complex with the protein.

When an acyclic form of the dimer is used to bend the DNA, the bending angle is small and the oligonucleotide doesn't bind the protein, further suggesting the importance of DNA bending for protein binding.