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 t he binding of a zinc-finger protein, i.e. poly(ADP-ribose)polymerase t o DNA nicks, activation of four resident catalytic activities leading to poly(ADP-ribose) synthesis, conversion of the polymerase into a pro tein modified with up to 28 variably sized ADP-ribose polymers, and ra pid degradation of polymerase-bound polymers by poly(ADP-ribose)glycoh ydrolase. This auto modification cycle catalyzes a transient and rever sible dissociation of histones from DNA. Shuttling of histones on the DNA allows selected other proteins, such as DNA helicase A and topoiso merase I, to gain access to DNA. Histone shuttling in vitro mimics nuc leosomal unfolding/refolding in vivo that accompanies the postincision al steps of DNA excision repair. Suppression of the automodification c ycle in mammalian cells prevents nucleosomal unfolding and nucleotide excision repair. (C) 1993 Wiley-Liss, Inc.