A cellular survival switch: poly(ADP-ribosyl)ation stimulates DNA repair and silences transcription

Poly(ADP-ribosyl)ation is a post-translational modification occurring in th e nucleus. The most abundant and best-characterized enzyme catalyzing this reaction, poly(ADP-ribose) polymerase 1 (PARP1), participates in fundamenta l nuclear events. The enzyme functions as molecular "nick sensor". It binds with high affinity to DNA single-strand breaks resulting in the initiation of its catalytic activity. Activated PARP1 promotes base excision repair. In addition, PARP1 modifies several transcription factors and thereby precl udes their binding to DNA, We propose that a major function of PARP1 includ es the silencing of transcription preventing expression of damaged genes. C oncomitant stimulation of DNA repair suggests that PARP1 acts as a switch b etween transcription and DNA repair. Another PARP-type enzyme, tankyrase, i s involved in the regulation of telomere elongation. Tankyrase modifies a t elomere-associated protein and thereby prevents it masking telomeric repeat s providing access of telomerase for telomere elongation. Therefore, poly(A DP-ribosyl)ation reactions may act as molecular switches in DNA metabolism. (C) 2001 John Wiley & Sons, Inc.