Roger Woodgate, Ph.D.
Section on DNA Replication, Repair, and Mutagenesis
Studies on DNA Replication, Repair, and Mutagenesis in Eukaryotic and Prokaryotic Cells
Under optimal conditions, the fidelity of DNA replication is extremely high. Indeed, it is estimated that, on average, only one error occurs for every 10 billion bases replicated. However, given that living organisms are continually subjected to a variety of endogenous and exogenous DNA-damaging agents, optimal conditions rarely prevail in vivo. While all organisms have evolved elaborate repair pathways to deal with such damage, the pathways rarely operate with 100% efficiency. Thus, the persisting DNA lesions are replicated, but with much lower fidelity than in undamaged DNA. Our aim is to understand the molecular mechanisms by which mutations are introduced into damaged DNA. The process, commonly referred to as translesion DNA synthesis (TLS), is facilitated by one or more members of the Y-family of DNA polymerases that are conserved from bacteria to humans. Based on phylogenetic relationships, Y-family polymerases may be broadly classified into five subfamilies; DinB-like (polIV/pol kappa-like) proteins are ubiquitous and found in all domains of life; in contrast, the Rev1-like, Rad30A (pol eta)-like, and Rad30B (pol iota)-like polymerases are found only in eukaryotes and the UmuC (polV)-like polymerases only in prokaryotes. We continue to investigate TLS in all three domains of life: bacteria, archaea, and eukaryotes.
Dr. Roger Woodgate has devoted his scientific career to understanding the molecular mechanisms of damage-induced mutagenesis in prokaryotes and eukaryotes. He received his Ph.D. from the University of Sussex in Brighton, England and for the past 29 years has worked at the National Institute of Child Health and Human Development.
Sale JE, Lehmann AR, Woodgate R. Y-family DNA polymerases and their role in tolerance of cellular DNA damage. Nat Rev Mol Cell Biol. 2012;13(3):141-52.
McDonald JP, Vaisman A, Kuban W, Goodman MF, Woodgate R. Mechanisms employed by Escherichia coli to prevent ribonucleotide incorporation into genomic DNA by Pol V. PLoS Genet. 2012;8(11):e1003030.
Vaisman A, McDonald JP, Huston D, Kuban W, Liu L, Van Houten B, Woodgate R. Removal of misincorporated ribonucleotides from prokaryotic genomes: an unexpected role for nucleotide excision repair. PLoS Genet. 2013;9(11):e1003878.
Donigan KA, Cerritelli SM, McDonald JP, Vaisman A, Crouch RJ, Woodgate R. Unlocking the steric gate of DNA polymerase η leads to increased genomic instability in Saccharomyces cerevisiae. DNA Repair (Amst). 2015;35:1-12.
McIntyre J, McLenigan MP, Frank EG, Dai X, Yang W, Wang Y, Woodgate R. Posttranslational Regulation of Human DNA Polymerase ι. J Biol Chem. 2015;290(45):27332-44.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Genetics and Genomics
This page was last updated on August 31st, 2019