Mutation induced by DNA damage: a many protein affair

Abstract

The survival of an organism depends on the exceptionally precise duplication of its genome. To achieve this precision, the DNA polymerase itself must have extraordinary accuracy. In addition, a variety of repair mechanisms are needed to remove DNA lesions ahead of the replication fork and to correct mistakes left behind by the replication machinery. Mechanisms must also exist to deal with the potentially catastrophic encounter of a DNA polymerase with a replicationblocking lesion. In this brief review, we will consider the mechanisms responsible for the replication skills of the polymerase and the sources of occasional failure, with an emphasis on the SOS response induced by a replication-blocking lesion. Under normal growth conditions, error frequencies in the duplication of the Escherichia coli genome are 10 9 to 10 -1° per base replicated. This high fidelity is achieved by a 3-step process: (1) the correct selection of the complementary deoxynucleoside triphosphate substrate during 5' --, 3' incorporation (base selection); (2) exonucleolytic 3' ~ 5' editing of a noncomplementary deoxynucleoside monophosphate misinserted at the end of the growing chain; (3) post-replicative mismatch repair. DNA polymerase III holoenzyme (pol III) is responsible for the majority of