Chromatin dynamics. Fast and slow modes of nucleosome movement revealed through psoralen binding and repair

Psoralen adducts, when formed in DNA at low frequencies that permit extensive survival of normal and repair-deficient cells, are found in both linker and core regions of nucleosomes, but are slightly enriched in the linker sites. The relative frequencies of adducts obtained with 5-methylisopsoralen and angelicin, which form only monoadducts, and 8-methoxypsoralen and trimethylpsoralen, which form monoadducts and cross-links, represent an enrichment in linker DNA that is approx. 2-3-fold higher per nucleotide than in core DNA. 5-Methylisopsoralen monoadducts, which are initially in linker DNA, become randomized during 12 h of growth. This suggests a slow lateral movement of nucleosomes with respect to DNA and implies that linker and core regions of DNA are not permanent assignments. Randomization of 5-methylisopsoralen adducts is independent of the synthesis of DNA, RNA, protein, or poly(ADP-ribose) and is also independent of DNA repair. Excision repair of these adducts, in contrast, causes rapid local changes in nucleosome conformation and an initial increase in staphylococcal nuclease sensitivity that reverts to the sensitivity of bulk chromatin in less than 1 h. Chromatin, therefore, can undergo at least two distinct dynamic changes under physiological conditions: a slow randomization of the nucleosomes with respect to DNA, and a rapid but transient local rearrangement to facilitate repair.