Abstract
Poly(ADP-ribose) is synthesized from NAD+ in the nuclei of eukaryotic cells and the activity of the chromatin-bound enzyme, poly(ADP-ribose) polymerase, is markedly stimulated by DNA strand breaks1–7. Recent studies suggest that poly(ADP-ribose) is associated with the repair of DNA damage8–10 and the process of cellular differentiation11,12. Hence, abnormalities in the metabolism of poly(ADP-ribose) could be aetiologically related to some of the human genetic disorders of DNA repair, especially those that are characterized by congenital and developmental anomalies. Defects in poly(ADP-ribose) metabolism could arise from abnormalities in the enzyme poly(ADP-ribose) polymerase, abnormalities in levels of its substrate NAD+, the proteins that act as acceptors for poly(ADP)-ribosylation or polymer stability. We have examined cells from patients with genetic disorders of DNA repair to determine whether they contain the enzyme poly(ADP-ribose) polymerase, whether the enzyme increases its activity in response to DNA damage and whether the cells maintain normal levels of NAD+. We demonstrate here that cells from patients having Fanconi's anaemia have lower NAD+ levels than cells from normal donors. This abnormality may contribute to the disorders of DNA repair and congenital anomalies that characterize this disease13,14.
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Berger, N., Berger, S. & Catino, D. Abnormal NAD+ levels in cells from patients with Fanconi's anaemia. Nature 299, 271–273 (1982). https://doi.org/10.1038/299271a0
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DOI: https://doi.org/10.1038/299271a0
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