TARGETING OF HISTONE TAILS BY POLY(ADP-RIBOSE)

After Zn2+ finger-mediated binding to a DNA break, poly(ADP-ribose) po lymerase becomes automodified with long polymers of ADP-ribose. These nucleic acid-like polymers may facilitate DNA repair by noncovalently interacting with neighboring proteins. Using a novel screening techniq ue, we have identified histones as the predominant poly(ADP-ribose)-bi nding species in human keratinocytes, rat hepatocytes, frog eggs, and yeast. Polymer binding is confined specifically to the histone domains responsible for DNA condensation, i.e. histone tails. Our results ind icate that polymers of ADP-ribose are targeted to sites of DNA strand breaks by poly(ADP-ribose) polymerase and subsequently function to alt er chromatin conformation through noncovalent interactions with histon e tails.