U-turn DNA bending by human mitochondrial transcription factor A.

Transcription factor A (TFAM) is involved in the transcription regulation, maintenance and compaction of the mitochondrial genome. Recent structural data on TFAM showed its mode of operation and clarified previous biochemical and genetic results. In solution, TFAM is highly dynamic. According to crystal structures of its complex with the cognate light-strand promoter (LSP) binding sequence, it intertwines and dramatically bends DNA, thereby allowing interactions with the transcription initiation machinery. Recent studies have shown TFAM sliding on non-specific DNA, which induces compaction by increasing DNA flexibility. Finally, the structural localization of disease-related TFAM mutations suggests functional impairment at the molecular level.