Dynamics of the Escherichia coli nucleotide excision repair system

Abstract

Ultraviolet light induced pyrimidine dimers in DNA are recognized and repaired by a number of unique cellular surveillance systems. At the highest level of complexity Escherichia coli (E. coli) has a uvr DNA repair system comprising the UvrA, UvrB and UvrC proteins responsible for incision. There are several preincision steps governed by this pathway which includes an ATP-dependent UvrA dimerization reaction required for UvrAB nucleoprotein formation. This complex formation driven by ATP binding, is associated with localized topological unwinding of DNA. This protein complex can catalyze an ATP-dependent 5'----3' directed strand displacement of D-loop DNA or short single strands annealed to a single stranded circular or linear DNA. This putative translocational process is arrested when damaged sites are encountered. The complex is now primed for dual incision catalyzed by UvrC. The remainder of the repair process involves UvrD (helicase II) and DNA polymerase I for a coordinately controlled "excision resynthesis" step accompanied by UvrABC turnover. Furthermore, it is proposed that levels of repair proteins can be regulated by proteolysis. UvrB is converted to truncated UvrB* by a stress induced protease which also acts at similar sites on the E. coli Ada protein. Although UvrB* can bind with UvrA to DNA it cannot participate in helicase or incision reactions. It is also a DNA-dependent ATPase.