<i>Mycobacterium tuberculosis</i> DNA repair helicase UvrD1 is activated by redox-dependent dimerization via a 2B domain cysteine
Ankita Chadda, Drake Jensen, Eric J. Tomko, Ana Ruiz Manzano, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Abstract
UvrD1 exists in monomer, dimer, and higher-order oligomeric forms, where dimerization is regulated by redox potential. We identify a 2B domain cysteine, conserved in many Actinobacteria, that underlies this effect. We also show that UvrD1 DNA-unwinding activity correlates specifically with the dimer population and is thus titrated directly via increasing positive (i.e., oxidative) redox potential. Consistent with the regulatory role of the 2B domain and the dimerization-based activation of DNA unwinding in UvrD family helicases, these results suggest that UvrD1 is activated under oxidizing conditions when it may be needed to respond to DNA damage during infection.