Title The RecA-NT homology motif in ImuB mediates the interaction with ImuA′, which is essential for DNA damage–induced mutagenesis /
Authors Santos, Joana A ; Timinskas, Kęstutis ; Ramudzuli, Atondaho A ; Lamers, Meindert H ; Venclovas, Česlovas ; Warner, Digby F ; Gessner, Sophia J
DOI 10.1016/j.jbc.2024.108108
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Is Part of Journal of biological chemistry.. Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. 2025, vol. 301, iss. 2, art. no. 108108, p. [1-11].. eISSN 1083-351X
Keywords [eng] antibiotic resistance ; DNA repair ; mutagenesis ; mutasome ; Mycobacterium tuberculosis ; protein–protein interaction
Abstract [eng] The mycobacterial mutasome—comprising ImuAʹ, ImuB, and DnaE2—has been implicated in DNA damage–induced mutagenesis in Mycobacterium tuberculosis. ImuB, which is predicted to enable mutasome function via its interaction with the β clamp, is a catalytically inactive Y-family DNA polymerase. Like some other members of the Y-family, ImuB features a recently identified amino acid motif with homology to the RecA N terminus (RecA-NT). Given the role of RecA-NT in RecA oligomerization, we hypothesized that ImuB RecA-NT mediates the interaction with ImuAʹ, an RecA homolog of unknown function. Here, we constructed a panel of imuB alleles in which the RecA-NT was removed or mutated. Our results indicate that RecA-NT is critical for the interaction of ImuB with ImuAʹ. A region downstream of RecA-NT, ImuB-C, appears to stabilize the ImuB–ImuAʹ interaction, but its removal does not prevent complex formation. In contrast, replacing two hydrophobic residues of RecA-NT, L378 and V383, disrupts the ImuAʹ–ImuB interaction. To our knowledge, this is the first experimental evidence suggesting a role for RecA-NT in mediating the interaction between a Y-family member and an RecA homolog.
Published Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology
Type Journal article
Language English
Publication date 2025
CC license CC license description