Mechanisms of tolerance to DNA lesions in mammalian cells

Abstract

In recent years it has become clear that different pathways are involved in the process of removing lesions from DNA. In spite of a continuous surveillance of the genetic integrity by repair enzymes, quite often lesions are not eliminated before the portion of the genome where they have been inserted is used for DNA replication or transcription. Actually, the number of unexcised lesions a cell can tolerate without significantly losing its capacity to reproduce is surprising. As an example, human fibroblasts from certain patients with the genetic disease xeroderma pigmentosum (XP)† are virtually unable to excise pyrimidine dimers, the major DNA lesion produced by short-wavelength UV light.