Accumulation of the cyclobutane thymine dimer in defined sequences of free and nucleosomal DNA

Abstract

Photochemical cyclobutane dimerization of adjacent thymines generates the major lesion in DNA caused by exposure to sunlight. Not all nucleotide sequences and structures are equally susceptible to this reaction or its potential to create mutations. Photostationary levels of the cyclobutane thymine dimer have now been quantified in homogenous samples of DNA reconstituted into nucleosome core particles to examine the basis for previous observations that such structures could induce a periodicity in dimer yield when libraries of heterogeneous sequences were used. Initial rate studies did not reveal a similar periodicity when a homogenous core particle was analyzed, but this approach examined only formation of this photochemically reversible cyclobutane dimer. Photostationary levels result from competition between dimerization and reversion and, as described in this study, still express none of the periodicity within two alternative core particles that was evident in heterogeneous samples. Such periodicity likely arises from only a limited set of sequences and structural environments that are not present in the homogeneous and well-characterized assemblies available to date.