دورية أكاديمية
Investigating the composition and recruitment of the mycobacterial ImuA′–ImuB–DnaE2 mutasome
| العنوان: | Investigating the composition and recruitment of the mycobacterial ImuA′–ImuB–DnaE2 mutasome |
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| المؤلفون: | Sophia Gessner, Zela Alexandria-Mae Martin, Michael A Reiche, Joana A Santos, Ryan Dinkele, Atondaho Ramudzuli, Neeraj Dhar, Timothy J de Wet, Saber Anoosheh, Dirk M Lang, Jesse Aaron, Teng-Leong Chew, Jennifer Herrmann, Rolf Müller, John D McKinney, Roger Woodgate, Valerie Mizrahi, Česlovas Venclovas, Meindert H Lamers, Digby F Warner |
| المصدر: | eLife, Vol 12 (2023) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | Mycobacterium tuberculosis, Mycobacterium smegmatis, induced mutagenesis, antibiotic resistance, anti-evolution, mutasome, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | A DNA damage-inducible mutagenic gene cassette has been implicated in the emergence of drug resistance in Mycobacterium tuberculosis during anti-tuberculosis (TB) chemotherapy. However, the molecular composition and operation of the encoded ‘mycobacterial mutasome’ – minimally comprising DnaE2 polymerase and ImuA′ and ImuB accessory proteins – remain elusive. Following exposure of mycobacteria to DNA damaging agents, we observe that DnaE2 and ImuB co-localize with the DNA polymerase III β subunit (β clamp) in distinct intracellular foci. Notably, genetic inactivation of the mutasome in an imuBAAAAGG mutant containing a disrupted β clamp-binding motif abolishes ImuB–β clamp focus formation, a phenotype recapitulated pharmacologically by treating bacilli with griselimycin and in biochemical assays in which this β clamp-binding antibiotic collapses pre-formed ImuB–β clamp complexes. These observations establish the essentiality of the ImuB–β clamp interaction for mutagenic DNA repair in mycobacteria, identifying the mutasome as target for adjunctive therapeutics designed to protect anti-TB drugs against emerging resistance. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/75628; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.75628 |
| URL الوصول: | https://doaj.org/article/9340d5204dad4cac96d701c78d904d63 |
| رقم الأكسشن: | edsdoj.9340d5204dad4cac96d701c78d904d63 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.75628 |