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Mycobacterial Topoisomerase IA Energetically Suffers From C-terminal Deletions

Balthrop, D.; Sigdel, D.; Mao, C.; Tse-Dinh, Y.-C.; Mills, M.

2024-09-09 biophysics
10.1101/2024.09.09.612055 bioRxiv
Show abstract

Type IA topoisomerases relieve torsional stress in DNA by a strand-passage mechanism, using the strain in the DNA to drive relaxation. The topoisomerase IAs of the Mycobacterium genus have distinct C-terminal domains which are crucial for successful strand-passage. We used single-molecule magnetic tweezers to observe supercoil relaxation by wild type Mycobacterium smegmatis topoisomerase IA and two C-terminal truncation mutants. We recorded distinct behaviors from each truncation mutant. We calculated the free energy stored in the DNA as it is twisted under force to examine the differences between the proteins. Based on our results, we propose a modified model of the strand-passage cycle.

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