The autosomal recessive genetic disease, Fanconi anaemia, is perceived as another manifestation of defective cellular DNA repair, just as in the autosomal recessive disease Xeroderma pigmentosum. The biochemistry and cellular biology of Xeroderma pigmentosum have been convincingly elucidated, but the same has not been true for Fanconi anaemia. In this review we consider the pleiotropic nature of Fanconi anaemia, its clinical and cellular variability and its genetic heterogeneity. We take into account the wealth of experimental findings available and offer a (...) novel hypothesis involving feedback control of DNA replication during S phase of the cell cycle to explain the basic defect in the disease. (shrink)

The autosomal recessive genetic disorder, Nijmegen Breakage Syndrome, is characterised by an excessively high risk for the development of lymphatic tumours and an extreme sensitivity towards ionising radiation. The most likely explanation for these characteristics, a deficiency in the repair of DNA lesions, has been greatly substantiated by the recent cloning of the gene mutated in Nijmegen Breakage Syndrome patients and the analysis of its protein product, nibrin. The direct involvement of this protein in the processing of DNA double strand (...) breaks caused by ionising radiation and those also necessary for normal DNA metabolism can be correlated with many of the cellular and clinical aspects of the disease, including the cancer predisposition of patients and their heterozygous relatives. BioEssays 21:649–656, 1999. © 1999 John Wiley & Sons, Inc. (shrink)