Challenging a paradigm: the role of DNA homology in tyrosine recombinase reactions.
A classical feature of the tyrosine recombinase family of proteins catalyzing site-specific recombination, as exemplified by the phage lambda integrase and the Cre and Flp recombinases, is the ability to recombine substrates sharing very limited DNA sequence identity. Decades of research have established the importance of this short stretch of identity within the core regions of the substrates. Since then, several new enzymes that challenge this paradigm have been discovered and require the role of sequence identity in site-specific recombination to be reconsidered. The integrases of the conjugative transposons such as Tn916, Tn1545, and CTnDOT recombine substrates with heterologous core sequences. The integrase of the mobilizable transposon NBU1 performs recombination more efficiently with certain core mismatches. The integration of CTX phage and capture of gene cassettes by integrons also occur by altered mechanisms. In these systems, recombination occurs between mismatched sequences by a single strand exchange. In this review, we discuss literature that led to the formulation of the current strand-swapping isomerization model for tyrosine recombinases. The review then focuses on recent developments on the recombinases that challenged the paradigm that was derived from the studies of early systems.
Rajeev
Lara
L
Department of Civil and Environmental Engineering, University of Washington, Seattle, Washington 98125, USA. lrajeev@u.washington.edu
Malanowska
Karolina
K
Gardner
Jeffrey F
JF
D000818:Animals; D020137:Base Pair Mismatch; D004251:DNA Transposable Elements / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D045522:Recombinases / Q000378:metabolism*; D011995:Recombination, Genetic; D012689:Sequence Homology, Nucleic Acid; D019895:Transposases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D045522:Recombinases; D014443:Tyrosine; D019895:Transposases