Physical and Functional Interactions between 3-Methyladenine DNA Glycosylase and Topoisomerase I in Mycobacteria

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Qiong Yang, Feng Huang, Lihua Hu, and Zheng-Guo He^*

National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; fax: +86-27-8728-0670; E-mail: he.zhengguo@hotmail.com; hezhengguo@mail.hzau.edu.cn

^* To whom correspondence should be addressed.

Received September 13, 2011; Revision received November 15, 2011

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DNA glycosylases play important roles in DNA repair in a variety of organisms, including humans. However, the function and regulation of these enzymes in the pathogenic bacterium Mycobacterium tuberculosis and related species are poorly understood. In the present study, the physical and functional interactions between 3-methyladenine DNA glycosylase (MAG) and topoisomerase I (TopA) in M. tuberculosis and M. smegmatis were characterized. MAG was found to inhibit the function of TopA in relaxing supercoiled DNA. In contrast, TopA stimulated the cleavage function of MAG on a damaged DNA substrate that contains hypoxanthine. The interaction between the two proteins was conserved between the two mycobacterial species. Several mutations in MAG that led to the loss of its interaction with and activity regulation of TopA were also characterized. The results of this study further elucidate glycosylase regulation in both M. smegmatis and M. tuberculosis.

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KEY WORDS: Mycobacterium tuberculosis, DNA glycosylase, topoisomerase I, DNA repair

DOI: 10.1134/S0006297912040098

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