Open AccessMycobacterium tuberculosis DNA repair helicase UvrD1 is activated by redox-dependent dimerization via a 2B domain cysteine
Author(s) -
Ankita Chadda,
Drake Jensen,
Eric J. Tomko,
Ana Ruiz Manzano,
Binh Nguyen,
Timothy M. Lohman,
Eric A. Galburt
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2114501119
Subject(s) - helicase , dna , dna repair , cysteine , dna damage , biology , pyrimidine dimer , biochemistry , escherichia coli , chemistry , enzyme , gene , rna
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 thatMt b UvrD1 is activated by the oxidative conditions imposed during infection.