ATP-dependent chromatin remodeling by the Cockayne syndrome B DNA repair-transcription-coupling factor

The Cockayne syndrome B protein (CSB) is required for coupling DNA excision repair to transcription in a process known as transcription-coupled repair (TCR). Cockayne syndrome patients show UV sensitivity and severe neurodeve lopmental abnormalities. CSB is a DNA-dependent ATPase of the SW12/SNF2 fam ily. SW12/SNF2-like proteins are implicated in chromatin remodeling during transcription. Since chromatin structure also affects DNA repair efficiency , chromatin remodeling activities within repair are expected. Here we used purified recombinant CSB protein to investigate whether it can remodel chro matin in vitro. We show that binding of CSB to DNA results in an alteration of the DNA double-helix conformation. In addition, we find that CSB is abl e to remodel chromatin structure at the expense of ATP hydrolysis. Specific ally, CSB can alter DNase I accessibility to reconstituted mononucleosome c ores and disarrange an array of nucleosomes regularly spaced on plasmid DNA . In addition, we show that CSB interacts not only with double-stranded DNA but also directly with core histones. Finally, intact histone tails play a n important role in CSB remodeling. CSB is the first repair protein found t o play a direct role in modulating nucleosome structure. The relevance of t his finding to the interplay between transcription and repair is discussed.