The RecA-NT homology motif in ImuB mediates the interaction with ImuA′, which is essential for DNA damage–induced mutagenesis
Year: 2024
Type: article
Abstract: The mycobacterial mutasome-comprising ImuA', 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 ImuA', 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 ImuA'. A region downstream of RecA-NT, ImuB-C, appears to stabilize the ImuB-ImuA' interaction, but its removal does not prevent complex formation. In contrast, replacing two hydrophobic residues of RecA-NT, L378 and V383, disrupts the ImuA'-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.
Source: Journal of Biological Chemistry
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,800
Funders: National Research Foundation, South African Medical Research Council, Universiteit Leiden, Lietuvos Mokslo Taryba, Leids Universitair Medisch Centrum, Norges Forskningsråd, Medical Research Council, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
OpenAlex ID: W4405532178