Transcriptional healing

The chemical structure of DNA in which our genes are stored is continuously attacked by an army of aggressive agents of endogenous or exogenous origin. These genotoxins—including ubiquitous, superficially innocuous agents such as water, oxygen, and sunlight—induce a variety of damages. The expanding spectrum of deleterious consequences ranges from mutagenic and carcinogenic effects to interruption of essential DNA transactions and ageing. An intricate network of DNA repair systems evolved to ensure faithful maintenance of the genome. One of the underappreciated effects of DNA injury is physical hampering of transcription. Any lesion obstructing progression of transcription functionally inactivates a gene copy. Although far from being understood, recent papers (Le Page et al., 2000; Yu et al., 2000 [May issue of Molecular Cell]) shed important new light on the solutions “nature” invented to overcome such roadblocks on the one-rail gene track. Multiple DNA repair systems seem to be linked to transcription in order to rescue transcription machinery that has collided with a lesion. However, first a specialized device must displace the stalled RNA polymerase before the DNA repair apparatus can reach the injured site of the gene. Disruption of the repair–transcription interconnection has severe clinical consequences. Here we will put the new findings into perspective.

• View at Publisher