Mycobacterium tuberculosis DNA repair helicase UvrD1 is activated by redox-dependent dimerization via a 2B domain cysteine

Abstract

Significance Mycobacterium tuberculosis ( Mtb ) is an intracellular pathogen that causes tuberculosis and is exposed to oxidative insults from immune system macrophages. Mtb UvrD1 plays a role in DNA repair during infection and has been suggested to function as a monomer. However, we find that UvrD1 can self-assemble, the balance between monomer and dimer depends on redox potential via a cysteine residue in the regulatory 2B domain, and unwinding activity is uniquely a property of the dimer. Our results provide direct evidence of the domain interface in these ubiquitous enzymes, reveal a subfamily of UvrD-like enzymes regulated by redox potential, and suggest that Mt b UvrD1 is activated by the oxidative conditions imposed during infection.