Binding of Human Mitochondrial Transcription Factor A, an HMG Box Protein, to a Four-Way DNA Junction

Ohno, Tetsuji; Umeda, Shuyo; Hamasaki, Naotaka; Kang, Dongchon

doi:10.1006/bbrc.2000.2656

Cited by 51 publications

(32 citation statements)

References 28 publications

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“…On the other hand, TFAM activates transcription by binding and bending specific sequences at HSP or LSP29. Like other HMG-box proteins, TFAM also recognizes tRNA and distorted structures, such as DNA/RNA-containing 4-way junctions3334, base bulges, cis-platinum adducts or damaged DNA3536. In the mitochondrial matrix TFAM levels are regulated by LON37.…”

mentioning

confidence: 99%

The human mitochondrial transcription factor A is a versatile G-quadruplex binding protein

Lyonnais

Tarrés-Solé

Rubio-Cosials

et al. 2017

Sci Rep

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The ability of the guanine-rich strand of the human mitochondrial DNA (mtDNA) to form G-quadruplex structures (G4s) has been recently highlighted, suggesting potential functions in mtDNA replication initiation and mtDNA stability. G4 structures in mtDNA raise the question of their recognition by factors associated with the mitochondrial nucleoid. The mitochondrial transcription factor A (TFAM), a high-mobility group (HMG)-box protein, is the major binding protein of human mtDNA and plays a critical role in its expression and maintenance. HMG-box proteins are pleiotropic sensors of DNA structural alterations. Thus, we investigated and uncovered a surprising ability of TFAM to bind to DNA or RNA G4 with great versatility, showing an affinity similar than to double-stranded DNA. The recognition of G4s by endogenous TFAM was detected in mitochondrial extracts by pull-down experiments using a G4-DNA from the mtDNA conserved sequence block II (CSBII). Biochemical characterization shows that TFAM binding to G4 depends on both the G-quartets core and flanking single-stranded overhangs. Additionally, it shows a structure-specific binding mode that differs from B-DNA, including G4-dependent TFAM multimerization. These TFAM-G4 interactions suggest functional recognition of G4s in the mitochondria.

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mentioning

confidence: 99%

The human mitochondrial transcription factor A is a versatile G-quadruplex binding protein

Lyonnais

Tarrés-Solé

Rubio-Cosials

et al. 2017

Sci Rep

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“…The cDNA coding for mature human TFAM (amino acid residues 42 to 246) and mature human TFAM-⌬C-HA (amino acid residues 42 to 221 and C-terminal HA tag) were inserted into the pProEXHTb vector (Gibco). The recombinant His-human TFAM and His-human TFAM-⌬C-HA were expressed in Escherichia coli BL21 cells and purified Ni 2ϩ -bound chelating Sepharose resin (Amersham Biosciences) as described previously (28,36). In vitro transcription reactions were performed with a cloned DNA fragments corresponding to nucleotides 1 to 477 of human mtDNA as previously described (10).…”

Section: Methodsmentioning

confidence: 99%

Architectural Role of Mitochondrial Transcription Factor A in Maintenance of Human Mitochondrial DNA

Kanki

Ohgaki

Gaspari

et al. 2004

Molecular and Cellular Biology

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273

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Mitochondrial transcription factor A (TFAM), a transcription factor for mitochondrial DNA (mtDNA) that also possesses the property of nonspecific DNA binding, is essential for maintenance of mtDNA. To clarify the role of TFAM, we repressed the expression of endogenous TFAM in HeLa cells by RNA interference. The amount of TFAM decreased maximally to about 15% of the normal level at day 3 after RNA interference and then recovered gradually. The amount of mtDNA changed closely in parallel with the daily change in TFAM while in organello transcription of mtDNA at day 3 was maintained at about 50% of the normal level. TFAM lacking its C-terminal 25 amino acids (TFAM-⌬C) marginally activated transcription in vitro. When TFAM-⌬C was expressed at levels comparable to those of endogenous TFAM in HeLa cells, mtDNA increased twofold, suggesting that TFAM-⌬C is as competent in maintaining mtDNA as endogenous TFAM under these conditions. The in organello transcription of TFAM-⌬C-expressing cells was no more than that in the control. Thus, the mtDNA amount is finely correlated with the amount of TFAM but not with the transcription level. We discuss an architectural role for TFAM in the maintenance of mtDNA in addition to its role in transcription activation.

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“…Likewise, the mouse homolog of Abf2, TFAM, also stabilizes the Holliday junctions in heart mtDNA (87). TFAM is known to bind four-way DNA junctions (122).…”

Section: Abf2 and Tfammentioning

confidence: 99%

Mechanism of Homologous Recombination and Implications for Aging-Related Deletions in Mitochondrial DNA

Chen

2013

Microbiol Mol Biol Rev

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SUMMARY Homologous recombination is a universal process, conserved from bacteriophage to human, which is important for the repair of double-strand DNA breaks. Recombination in mitochondrial DNA (mtDNA) was documented more than 4 decades ago, but the underlying molecular mechanism has remained elusive. Recent studies have revealed the presence of a Rad52-type recombination system of bacteriophage origin in mitochondria, which operates by a single-strand annealing mechanism independent of the canonical RecA/Rad51-type recombinases. Increasing evidence supports the notion that, like in bacteriophages, mtDNA inheritance is a coordinated interplay between recombination, repair, and replication. These findings could have profound implications for understanding the mechanism of mtDNA inheritance and the generation of mtDNA deletions in aging cells.

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Binding of Human Mitochondrial Transcription Factor A, an HMG Box Protein, to a Four-Way DNA Junction

Cited by 51 publications

References 28 publications

The human mitochondrial transcription factor A is a versatile G-quadruplex binding protein

The human mitochondrial transcription factor A is a versatile G-quadruplex binding protein

Architectural Role of Mitochondrial Transcription Factor A in Maintenance of Human Mitochondrial DNA

Mechanism of Homologous Recombination and Implications for Aging-Related Deletions in Mitochondrial DNA

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