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Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation

Author

Listed:
  • Huu B. Ngo

    (California Institute of Technology
    Howard Hughes Medical Institute, California Institute of Technology)

  • Geoffrey A. Lovely

    (California Institute of Technology
    California Institute of Technology)

  • Rob Phillips

    (California Institute of Technology
    California Institute of Technology)

  • David C. Chan

    (California Institute of Technology
    Howard Hughes Medical Institute, California Institute of Technology)

Abstract

TFAM (transcription factor A, mitochondrial) is a DNA-binding protein that activates transcription at the two major promoters of mitochondrial DNA (mtDNA)—the light strand promoter (LSP) and the heavy strand promoter 1 (HSP1). Equally important, it coats and packages the mitochondrial genome. TFAM has been shown to impose a U-turn on LSP DNA; however, whether this distortion is relevant at other sites is unknown. Here we present crystal structures of TFAM bound to HSP1 and to nonspecific DNA. In both, TFAM similarly distorts the DNA into a U-turn. Yet, TFAM binds to HSP1 in the opposite orientation from LSP explaining why transcription from LSP requires DNA bending, whereas transcription at HSP1 does not. Moreover, the crystal structures reveal dimerization of DNA-bound TFAM. This dimerization is dispensable for DNA bending and transcriptional activation but is important in DNA compaction. We propose that TFAM dimerization enhances mitochondrial DNA compaction by promoting looping of the DNA.

Suggested Citation

  • Huu B. Ngo & Geoffrey A. Lovely & Rob Phillips & David C. Chan, 2014. "Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation," Nature Communications, Nature, vol. 5(1), pages 1-12, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4077
    DOI: 10.1038/ncomms4077
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    Cited by:

    1. Hyun Huh & Jiayu Shen & Yogeeshwar Ajjugal & Aparna Ramachandran & Smita S. Patel & Sang-Hyuk Lee, 2024. "Sequence-specific dynamic DNA bending explains mitochondrial TFAM’s dual role in DNA packaging and transcription initiation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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