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Lichtarge Computational Biology Lab

Houston, Texas

Lichtarge Computational Biology Lab
Lichtarge Computational Biology Lab
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Separation of Recombination and SOS Response in
E. coli RecA Suggests LexA Interaction Sites

Adikesavan AK, Katsonis P, Marciano DC, Lua RC, Herman C, Lichtarge O.

PLoS Genetics. In Press - July, 2011.

Abstract

RecA plays a key role in homologous recombination, the induction of the DNA
damage response through LexA cleavage and the activity of error-prone
polymerase in E. coli. RecA interacts with multiple partners to achieve this
pleiotropic role, but the structural location and sequence determinants
involved in these multiple interactions remain mostly unknown. Here, in a
first application to prokaryotes, Evolutionary Trace (ET) analysis identifies
clusters of evolutionarily important surface amino acids involved in RecA
functions. Some of these clusters match the known ATP binding, DNA binding,
and RecA-RecA homo-dimerization sites, but others are novel. Mutation
analysis at these sites disrupted either recombination or LexA cleavage. This
highlights distinct functional sites specific for recombination and DNA
damage response induction. Finally, our analysis reveals a composite site for
LexA binding and cleavage, which is formed only on the active RecA filament.
These new sites can provide new drug targets to modulate one or more RecA
functions, with the potential to address the problem of evolution of
antibiotic resistance at its root.