Structural Biology of DNA (6-4) Photoproducts Formed by Ultraviolet Radiation and Interactions with Their Binding Proteins

Abstract

Exposure to the ultraviolet component of sunlight causes DNA damage, which subsequently leads to mutations, cellular transformation, and cell death. DNA photoproducts with (6-4) pyrimidine-pyrimidone adducts are more mutagenic than cyclobutane pyrimidine dimers. These lesions must be repaired because of the high mutagenic potential of (6-4) photoproducts. We here reviewed the structures of (6-4) photoproducts, particularly the detailed structures of the (6-4) lesion and (6-4) lesion-containing double-stranded DNA. We also focused on interactions with their binding proteins such as antibody Fabs, (6-4) photolyase, and nucleotide excision repair protein. The (6-4) photoproducts that bound to these proteins had common structural features: The 5'-side thymine and 3'-side pyrimidone bases of the T(6-4)T segment were in half-chair and planar conformations, respectively, and both bases were positioned nearly perpendicularly to each other. Interactions with binding proteins showed that the DNA helices flanking the T(6-4)T segment were largely kinked, and the flipped-out T(6-4)T segment was recognized by these proteins. These proteins had distinctive binding-site structures that were appropriate for their functions.