Damage inducible mutagenesis: recent insights into the activities of the Umu family of mutagenesis proteins.

Despite our advances, much remains to be elucidated about the molecular mechanisms of damage inducible mutagenesis. Although some aspects of the intricate protein interactions that lead to the formation of the mutasome have been determined, the precise nature of the interactions between pol III and the UmuD'C-RecA proteins remains entirely speculative. Further progress will depend on the development of a completely reconstituted, cell free lesion bypass system in vitro, as well as structural modelling of the mutasome in its entirety before we understand how error prone translesion DNA synthesis is achieved. Even if a structural homologue of the Escherichia coli mutasome does not exist in higher organisms, it seems quite likely that a functionally homologous mutagenic pathway will indeed be found. Such an active mutagenic process in animal cells would certainly have significant implications for our understanding of the mechanisms of genetic instability, as well as of human carcinogenesis and other pathologies associated with the formation of mutations in DNA.