DUAL FUNCTIONS OF DNA-REPAIR GENES - MOLECULAR, CELLULAR, AND CLINICAL IMPLICATIONS

The complex series of DNA repair pathways that are used to repair dama ge to cellular DNA employ many different proteins. A substantial numbe r of these have second functions. Defects in these multifunctional pro teins in man can lead to widely differing clinical phenotypes dependin g on which of the functions is affected. This is illustrated most clea rly in the transcription factor TFIIH, which is involved in both basal transcription and nucleotide excision repair. Different mutations in genes encoding TFIIH subunits can result in the highly cancer-prone re pair disorder xeroderma pigmentosum, or the noncancer-prone multisyste m disorder trichothiodystrophy, the features of which are probably a c onsequence of abnormalities in transcription. The involvement of repai r proteins in other processes also poses interesting evolutionary ques tions. BioEssays 20.146-155, 1998. (C) 1998 John Wiley & Sons, Inc.