La réparation de l'ADN au centre de la biologie de la cellule
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All living cells must maintain the integrity of their genetic information in order to function normally. The genetic stability is insured by numerous repair pathways which counteract the deleterious consequences of DNA lesions produced by a variety of endogenous or exogenous geno-toxics. Among them, UV light is a potent source of hasards in man. The fundamental role of repair pathways is attested by the existence of several human diseases where UV-hypersensitivity due to repair deficiency is associated with cancer-proneness (Xeroderma pigmentosum) or with various other clinical defects (Cockayne's syndrome or trichothiodystrophy). These rare, genetically-transmitted disorders have been used to clone several human DNA repair genes. The study of these genes as well as those involved in DNA repair of drosophila, yeast or bacteria allows us to draw a picture of how excision DNA repair is working in man. A very close relationship between transcription process and preferential repair of active genes has been demonstrated using some of these patients cells. Several of these repair genes code for DNA/RNA helicases which, at least for one, also belong to basal transcription complex. Defects in these genes are also involved in neurological disorders and in the initiation of carcinogenesis. Molecular analysis of the regulation of these genes will give us fondamental information on some diseases and on the possible use of gene therapy.
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Sarasin, A., La réparation de l'ADN au centre de la biologie de la cellule, Med Sci (Paris), 1994, Vol. 10, N° 1; p.951-2