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Spatially directed assembly of a heterotetrameric Cre-Lox synapse restricts recombination specificity.


ABSTRACT: The pseudo-fourfold homotetrameric synapse formed by Cre protein and target DNA restricts site-specific recombination to sequences containing dyad-symmetric Cre-binding repeats. Mixtures of engineered altered-specificity Cre monomers can form heterotetramers that recombine nonidentical asymmetric sequences, allowing greater flexibility for target site selection in the genome of interest. However, the variety of tetramers allowed by random subunit association increases the chances of unintended reactivity at nontarget sites. This problem can be circumvented by specifying a unique spatial arrangement of heterotetramer subunits. By reconfiguring intersubunit protein-protein contacts, we directed the assembly of two different Cre monomers, each having a distinct DNA sequence specificity, in an

SUBMITTER: Gelato KA 

PROVIDER: S-EPMC2418607 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature