Phosphatases, DNA Damage Checkpoints and Checkpoint Deactivation

J. Heideker, E.T. Lis, F.E. Romesberg, Cell Cycle (2007) 6:3058-3064.
pubpic2007heidekerWe review progress toward understanding the functions of phosphatases in checkpoint deactivation in S. cerevisiae, focusing on the non-redundant roles of the type 2A phosphatase Pph3 and the PP2C phosphatases Ptc2 and Ptc3 in the deactivation of Rad53.


Structural and initial biological analysis of synthetic arylomycin A2

T.C. Roberts, P.A. Smith, R.T. Cirz, F.E. Romesberg, J. Am. Chem. Soc. (2007) 129:15830-15838.
pubpic2007robertsWe report the synthesis and characterization of arylomycin natural products. These studies help identify the determinants of the biological activity of arylomycin A2 and should aid in the design of analogs to further explore and develop this novel class of antibiotic.


Controlling mutation: intervening in evolution as a therapeutic strategy

R.T. Cirz and F.E. Romesberg, Crit. Rev. Biochem. Mol. Biol. (2007) 42:341-354.
pubpic2007cirzWe review what is known about induced mutagenesis in bacteria as well as evidence that it contributes to the evolution of antibiotic resistance and we discuss the possibility that components of induced mutation pathways might be targeted for inhibition as a novel therapeutic strategy to prevent the evolution of antibiotic resistance.


Combating bacteria and drug-resistance by inhibiting mechanisms of persistence and adaptation

P.A. Smith and F.E. Romesberg, Nat. Chem. Biol. (2007) 3:549-556.
pubpic2007smithAn improved understanding of bacterial stress responses and evolution suggests that in the ability of bacteria to survive antibiotic therapy either by transiently tolerating antibiotics or by evolving resistance may require specific biochemical processes. We review early efforts toward inhibiting these processes as a means to prolong the efficacy of current antibiotics and provide an alternative to escalating the current arms race between antibiotics and bacterial resistance.


Polymerase recognition and stability of fluoro substituted pyridone nucleobase analogs

G.T. Hwang, A.M. Leconte, F.E. Romesberg, ChemBioChem. (2007) 8:1606-1611.
pubpic2007hwangWe synthesize and characterize three fluoro-substituted pyridone nucleoside analogues. Generally, we find that the specific fluorine substitution pattern of the analogs has little impact on unnatural pair or mispair stability, but does significantly increase the rate at which the pyridone-based unnatural base pairs are extended.


Efforts toward expansion of the genetic alphabet: Structure and replication of unnatural base pairs

S. Matsuda, J.D. Fillo, A.A. Henry, P. Rai, S. J. Wilkens, T.J. Dwyer, B.H. Geierstanger, D.E. Wemmer, P.G. Schultz, G. Spraggon, F.E. Romesberg,J. Am Chem. Soc. (2007) 129:10466-10473.
pubpic2007bmatsudaWe examine the structure of DNA duplexes containing either the d3FB or dPICS self-pairs. We find that the large aromatic rings of the dPICS nucleobases pair in an intercalative manner within duplex DNA, while the d3FB nucleobases interact in an edge-on manner, much closer in structure to natural base pairs.


AID-initiated purposeful mutations in immunoglobulin genes

M.F. Goodman, M.D. Schaarf, F.E. Romesberg, Adv. Immunol. (2007) 94:127-155.
pubpic2007goodmanWe review the role of activation-induced cytidine deaminase (AID) in the complex process of somatic hypermutation (SHM) and present recent advances in experimental methods to characterize antibody dynamics as a function of SHM to help elucidate the role that the AID-induced mutations play in tailoring molecular recognition.