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2020•FEBS LettersOpen access

Mycobacterium tuberculosis TetR family transcriptional regulator Rv1019 is a negative regulator of the mfd‐mazG operon encoding DNA repair proteins

Akhil Raj Pushparajan, Ranjit Ramachandran, Jijimole Gopi Reji, Ramakrishnan Ajay Kumar

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Abstract

Rv1019, a member of an uncharacterized tetracycline resistance regulator family of transcriptional regulators of Mycobacterium tuberculosis H37Rv, was found to be differentially expressed during dormancy and reactivation in vitro. In this study, we show that this protein binds to its own promoter and acts as a negative regulator of its own expression. It forms dimers in vitro which is essential for the DNA binding activity. We also show that Rv1019 and downstream genes Rv1020 (mfd) and Rv1021 (mazG) are cotranscribed. Constitutive expression of Rv1019 in M. smegmatis downregulated MSMEG_5423 (mfd) and MSMEG_5422 (mazG), suggesting that Rv1019 negatively regulates these downstream genes which encode key proteins involved in DNA repair. M. smegmatis expressing Rv1019 was found to be sensitive to DNA-damaging environments, suggesting its role in regulating the DNA damage response in mycobacterium.

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Rv1019, a member of an uncharacterized tetracycline resistance regulator family of transcriptional regulators of Mycobacterium tuberculosis H37Rv, was found to be differentially expressed during dormancy and reactivation in vitro. In this study, we show that this protein binds to its own promoter and acts as a negative regulator of its own expression. It forms dimers in vitro which is essential for the DNA binding activity. We also show that Rv1019 and downstream genes Rv1020 (mfd) and Rv1021 (mazG) are cotranscribed. Constitutive expression of Rv1019 in M. smegmatis downregulated MSMEG_5423 (mfd) and MSMEG_5422 (mazG), suggesting that Rv1019 negatively regulates these downstream genes which encode key proteins involved in DNA repair. M. smegmatis expressing Rv1019 was found to be sensitive to DNA-damaging environments, suggesting its role in regulating the DNA damage response in mycobacterium.

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Available abstract

Rv1019, a member of an uncharacterized tetracycline resistance regulator family of transcriptional regulators of Mycobacterium tuberculosis H37Rv, was found to be differentially expressed during dormancy and reactivation in vitro. In this study, we show that this protein binds to its own promoter and acts as a negative regulator of its own expression. It forms dimers in vitro which is essential for the DNA binding activity. We also show that Rv1019 and downstream genes Rv1020 (mfd) and Rv1021 (mazG) are cotranscribed. Constitutive expression of Rv1019 in M. smegmatis downregulated MSMEG_5423 (mfd) and MSMEG_5422 (mazG), suggesting that Rv1019 negatively regulates these downstream genes which encode key proteins involved in DNA repair. M. smegmatis expressing Rv1019 was found to be sensitive to DNA-damaging environments, suggesting its role in regulating the DNA damage response in mycobacterium.

Key concepts: TetR, Regulator, Operon, Mycobacterium tuberculosis, Transcriptional regulation, DNA, Genetics, Biology

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Mycobacterium tuberculosis TetR family transcriptional regulator Rv1019 is a negative regulator of the mfd‐mazG operon encoding DNA repair proteins — Research Paper | ScholarLens