The Stalling of Transcription at Abasic Sites Is Highly Mutagenic

Abstract

Abasic (AP) sites represent one of the most frequently formed lesions in DNA. Here, we examine the consequences of the stalling of RNA polymerase II at AP sites in DNA in Saccharomyces cerevisiae. A severe inhibition of transcription occurs in strains that are defective in the removal of AP sites and that also lack the RAD26 gene, a homolog of the human Cockayne syndrome group B (CSB) gene, and, importantly, a dramatic rise in mutagenesis is incurred in such strains. From the various observations presented here, we infer that the stalling of transcription at AP sites is highly mutagenic.

ACKNOWLEDGMENTS

This work was supported by National Institutes of Health grants CA35035 and CA41261. Sequencing of can1 ^r mutations was done in the Molecular Biology Core Laboratory, which is supported by NIEHS Center grant P30-ES06676.