Identification of determinants of high-fidelity DNA synthesis in Mycobacterium smegmatis DnaE1 through in silico and in vivo approaches.

ABSTRACT: Drug resistance in Mycobacterium tuberculosis presents a major challenge in tuberculosis treatment, highlighting the need to understand the underlying mechanisms. DNA replication plays an important role in the acquisition of drug resistance, and the expression of the DNA polymerase DnaE2 during adverse conditions has been associated with increased mutation rates. Here, we investigate the functional differences between the high-fidelity replicative DNA polymerase DnaE1 and the predicted error-prone DNA polymerase DnaE2, focusing on which amino acid changes affect polymerase fidelity. For this, we identify potential fidelity-altering positions using a two-entropies sequence analysis combined with experimental validation to test whether changes of these positions affect the mutation rates. We

SUBMITTER: Kuin RCM 

PROVIDER: S-EPMC12641269 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature