Structural Studies of the Lagging-Strand Processivity Switch of Thermus thermophilus
I am particularly interested in resolving the structural basis for the switch from a processive to a distributive mode of DNA replication during Okazaki fragment synthesis on the lagging strand. To that end, we are pursuing the structures of the DNA polymerase III alpha and tau subunits in complex with relevant substrates. Currently, we have solved structures of the unliganded DNA polymerase III alpha subunit as well as the alpha subunit in complex with DNA substrate and incoming nucleotide.
Above is a view of the crystal structure of a ternary complex of the DNA polymerase III alpha subunit from Thermus aquaticus (From: Wing et al., (2008) JMB. 382(4): 859-869).
Structural Studies of the Prokaryotic Replisome
I am also interested in determining how the components of the replisome (dnaB helicase, primase, and DNA polymerase III holoenzyme) interact during DNA replication. As such, we are also pursuing complexes of these components with a key focus on isolating a stable complex of the dnaB helicase, the clamp loader, and the DNA polymerase III alpha subunit.
Selected Publications
Wing, R.A.*, Bailey, S.*, and Steitz, T.A. (2008). Insights into the Replisome from the Structure of a Ternary Complex of the DNA Polymerase III alpha-subunit J. Mol. Biol. 382(4): 859-869 (PubMed).
Bailey, S., Wing, R.A., and Steitz, T.A. (2006). The Structure of T. aquaticus DNA Polymerase III is distinct from eukaryotic replicative DNA polymerases. Cell 126(5): 893-904. (PubMed).
* These authors contributed equally to this work