Andrew Mercer

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Site-specific recombinases are powerful tools for genome engineering. Hyperactivated variants of the resolvase/invertase family of serine recombinases function without accessory factors, and thus can be re-targeted to sequences of interest by replacing native DNA-binding domains (DBDs) with engineered zinc-finger proteins (ZFPs). However, imperfect(More)
The development of new methods for gene addition to mammalian genomes is necessary to overcome the limitations of conventional genetic engineering strategies. Although a variety of DNA-modifying enzymes have been used to directly catalyze the integration of plasmid DNA into mammalian genomes, there is still an unmet need for enzymes that target a single(More)
Transcription activator-like effector (TALE) proteins can be designed to bind virtually any DNA sequence. General guidelines for design of TALE DNA-binding domains suggest that the 5'-most base of the DNA sequence bound by the TALE (the N0 base) should be a thymine. We quantified the N0 requirement by analysis of the activities of TALE transcription factors(More)
A package of Fortran programs has been developed that permits a user to interactively design and test array grammars. The user can control the rule selection procedure in a derivation or parse, using weighted programming matrices; he also has a choice of instance selection schemes (raster, random, parallel). Examples are given involving array languages(More)
We demonstrate site-specific reporter labeling of proteins within live cells. By accessing the coenzyme A (CoA) metabolic pathway with a cell-permeable pantetheine analogue, we deliver CoA-bound reporter molecules for post-translational protein modification in vivo. These methods may be applied to natural product pathway manipulation as well as applications(More)
Routine manipulation of cellular genomes is contingent upon the development of proteins and enzymes with programmable DNA sequence specificity. Here we describe the structure-guided reprogramming of the DNA sequence specificity of the invertase Gin from bacteriophage Mu and Tn3 resolvase from Escherichia coli. Structure-guided and comparative sequence(More)
Transcription activator-like effector (TALE) proteins can be designed to bind virtually any DNA sequence. General guidelines for design of TALE DNA-binding domains suggest that the 50-most base of the DNA sequence bound by the TALE (the N0 base) should be a thymine. We quantified the N0 requirement by analysis of the activities of TALE transcription factors(More)
Nature has developed a remarkable strategy to isolate metabolites from the milieu of the cell for chemical modification through the use of carrier proteins. Common to both primary and secondary metabolic pathways, acyl-carrier proteins constitute a conserved protein architecture which mediate the biosynthesis of a variety of metabolic products. Analogies(More)
In vivo carrier protein tagging has recently become an attractive target for the site-specific modification of fusion systems and new approaches to natural product proteomics. A detailed study of pantetheine analogues was performed in order to identify suitable partners for covalent protein labeling inside living cells. A rapid synthesis of pantothenamide(More)
The serine recombinases are a diverse family of modular enzymes that promote high-fidelity DNA rearrangements between specific target sites. Replacement of their native DNA-binding domains with custom-designed Cys₂-His₂ zinc-finger proteins results in the creation of engineered zinc-finger recombinases (ZFRs) capable of achieving targeted genetic(More)