BIOMEDICINE: Feverish Fallout

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Science  16 Mar 2001:
Vol. 291, Issue 5511, pp. 2049e-2051e
DOI: 10.1126/science.291.5511.2049e

Temperature-sensitive mutations have been an invaluable research tool in genetic studies of organisms such as bacteria, yeast, and fruit flies. Following up on some unusual features of patients afflicted with a rare genetic disorder, Vermeulen et al. show that temperature- sensitive mutations occur in humans as well and can affect fundamental mechanisms of gene regulation.

Patients with trichothiodystrophy (TDD) display a wide spectrum of medical problems, including mild mental retardation, brittle hair and nails, and scaling of the skin. This condition is caused by mutations in the XPD gene, which encodes a component of the transcription and DNA repair complex TFIIH. Vermeulen et al. studied four TTD patients who had undergone transient hair loss while they were suffering from a fever. Cell culture analyses revealed that the XPD mutations in these patients destabilized TFIIH and disrupted its transcriptional and DNA repair activity at 41°C. The authors postulate that the fever-induced hair loss was induced by a transient suppression of the synthesis of proteins that cross-link keratin filaments, which caused the base of the hair fiber to become very fragile.—PAK

Acknowledgments

Nature Genet. 27, 299 (2001).

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