UV damage to DNA strongly influences its rotational setting on the histone surface of reconstituted nucleosomes.

Abstract

The major photoproduct formed in DNA, following absorption of ultraviolet (UV) light, is the cis-syn cyclobutane pyrimidine dimer (CPD). Formation of CPDs in DNA packaged into chromatin prior to UV irradiation results in a striking preference for these photoproducts to be oriented away from the histone surface in nucleosomes (Gale, J. M., Nissen, K. A., and Smerdon, M. J. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 6644-6648). In this report, we show that formation of nucleosomes onto UV-irradiated DNA results in a similar distribution of these photoproducts, indicating that preexisting CPDs in the DNA molecule can influence its rotational setting on the histone surface during nucleosome formation. This bias is less pronounced in the central three helical turns encompassing the dyad axis of nucleosomes, where the helix is overwound (10.7 bases/turn) relative to the "outer" portion of core DNA (10.0 bases/turn). Such a change in the rotational setting of DNA on the surface of newly formed nucleosomes could expose normally inaccessible DNA sequences to factors which control DNA processing.