Histone shuttle driven by the automodification cycle of poly(ADP‐ribose) polymerase

In mammalian cells, the incision step of DNA excision repair triggers a dramatic metabolic response in chromatin. The reaction starts with the binding of a zinc‐finger protein, i.e. poly‐(ADP‐ribose)polymerase to DNA nicks, activation of four resident catalytic activities leading to poly(ADP‐ribose) synthesis, conversion of the polymerase into a protein modified with up to 28 variably sized ADP‐ribose polymers, and rapid degradation of polymerase‐bound polymers by poly(ADP‐ribose)glycohydrolase. This automodification cycle catalyzes a transient and reversible dissociation of histones from DNA. Shuttling of histones on the DNA allows selected other proteins, such as DNA helicase A and topoisomerase I, to gain access to DNA. Histone shuttling in vitro mimics nucleosomal unfolding/refolding in vivo that accompanies the postincisional steps of DNA excision repair. Suppression of the automodification cycle in mammalian cells prevents nucleosomal unfolding and nucleotide excision repair. © 1993 Wiley‐Liss, Inc.