Mitochondrial transcription factor A (TFAM) has 5′-deoxyribose phosphate lyase activity in vitro

Zhao, Wenxin; Hussen, Adil S.; Freudenthal, Bret D.; Suo, Zucai; Zhao, Linlin

doi:10.1016/j.dnarep.2024.103666

DNA Repair

2024

DOI: 10.1016/j.dnarep.2024.103666

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Mitochondrial transcription factor A (TFAM) has 5′-deoxyribose phosphate lyase activity in vitro

Wenxin Zhao,

Adil S. Hussen,

Bret D. Freudenthal

et al.

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2024

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Cited by 2 publications

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The viable but non-culturable (VBNC) status of Shewanella putrefaciens (S. putrefaciens) with thermosonication (TS) treatment

Jiang,

Wang,

Bai

et al. 2024

Ultrasonics Sonochemistry

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The viable but non-culturable (VBNC) status of Shewanella putrefaciens (S. putrefaciens) with thermosonication (TS) treatment

Jiang,

Wang,

Bai

et al. 2024

Ultrasonics Sonochemistry

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DNA sequence and lesion-dependent mitochondrial transcription factor A (TFAM)-DNA-binding modulates DNA repair activities and products

Urrutia,

Chen,

Tang

et al. 2024

Nucleic Acids Research

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Mitochondrial DNA (mtDNA) is indispensable for mitochondrial function and is maintained by DNA repair, turnover, mitochondrial dynamics and mitophagy, along with the inherent redundancy of mtDNA. Base excision repair (BER) is a major DNA repair mechanism in mammalian mitochondria. Mitochondrial BER enzymes are implicated in mtDNA-mediated immune response and inflammation. mtDNA is organized into mitochondrial nucleoids by mitochondrial transcription factor A (TFAM). The regulation of DNA repair activities by TFAM-DNA interactions remains understudied. Here, we demonstrate the modulation of DNA repair enzymes by TFAM concentrations, DNA sequences and DNA modifications. Unlike previously reported inhibitory effects, we observed that human uracil-DNA glycosylase 1 (UNG1) and AP endonuclease I (APE1) have optimal activities at specific TFAM/DNA molar ratios. High TFAM/DNA ratios inhibited other enzymes, OGG1 and AAG. In addition, TFAM reduces the accumulation of certain repair intermediates. Molecular dynamics simulations and DNA-binding experiments demonstrate that the presence of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in certain sequence motifs enhances TFAM-DNA binding, partially explaining the inhibition of OGG1 activity. Bioinformatic analysis of published 8-oxodG, dU, and TFAM-footprint maps reveals a correlation between 8-oxodG and TFAM locations in mtDNA. Collectively, these results highlight the complex regulation of mtDNA repair by DNA sequence, TFAM concentrations, lesions and repair enzymes.

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Mitochondrial transcription factor A (TFAM) has 5′-deoxyribose phosphate lyase activity in vitro

Cited by 2 publications

References 51 publications

The viable but non-culturable (VBNC) status of Shewanella putrefaciens (S. putrefaciens) with thermosonication (TS) treatment

The viable but non-culturable (VBNC) status of Shewanella putrefaciens (S. putrefaciens) with thermosonication (TS) treatment

DNA sequence and lesion-dependent mitochondrial transcription factor A (TFAM)-DNA-binding modulates DNA repair activities and products

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