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

Environ Mol Mutagen. 1993;22(4):278-82. doi: 10.1002/em.2850220417.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA / metabolism
  • DNA Repair / physiology
  • Glycoside Hydrolases / metabolism
  • Histones / metabolism*
  • Humans
  • Models, Genetic
  • Poly(ADP-ribose) Polymerases / metabolism*

Substances

  • Histones
  • DNA
  • Poly(ADP-ribose) Polymerases
  • Glycoside Hydrolases
  • poly ADP-ribose glycohydrolase