A plethora of lesion-replicating DNA polymerases
- Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2725 USA
This extract was created in the absence of an abstract.
Lesions in DNA often pose considerable impediments to genome duplication. To overcome this block to DNA replication, cells utilize specialized accessory factors that allow the synthesis of nascent DNA chains opposite the blocking lesion. Recent studies suggest that many of the key participants in translesion DNA synthesis belong to a large family of structurally related proteins that are found in prokaryotes, archaea, and eukaryotes. Phylogenetic analysis of these proteins suggests that they can be subdivided broadly into four groups typified by Escherichia coli UmuC, E. coli DinB, Saccharomyces cerevisiae Rev1, and the S. cerevisiae Rad30 protein. In the past, the molecular mechanism of translesion DNA synthesis has been one of the major unsolved problems in DNA repair. In the last 12 months, however, we have witnessed rapid development in our understanding of this fascinating process, with the discovery that E. coli UmuC, DinB, S. cerevisiaeRad30, and a human homolog of Rad30 are all novel DNA polymerases, most of which are capable of replicating damaged DNA (Tang et al. 1998,1999; Johnson et al. 1999b; Masutani et al. 1999a; Wagner et al. 1999). These findings suggest that the process of translesion DNA synthesis is conserved from bacteria to humans (Fig. ).
Conserved mechanism of translesion DNA synthesis fromE. coli and S. cerevisiae to humans. The underlying premise of this model is that the cell’s highly processive replicase, unable to traverse the blocking lesion, dissociates from the template at the site of the lesion and is replaced by one of the distributive lesion-replicating polymerases described herein. These polymerases add 1 or 2 nucleotides to the nascent DNA chain opposite the lesion and, as a consequence, alleviate the kinetic block to replication. Once this is achieved, the cell’s main replicase is able to reassemble on the 3′ …
