Abstract
ADP–ribosyl transferase (ADPRT) is a DNA-dependent nuclear enzyme which covalently attaches ADP–ribose moieties derived from NAD to proteins to form mono- or poly-ADP–ribosyl derivatives1,2. ADPRT activity is strongly stimulated by breaks in DNA3,4 and the enzyme is required for efficient DNA repair5–7. Several reports have suggested that the metabolism of poly- or mono-(ADP–ribose) might also be involved in differentiation in various eukaryotes1,2,8–12. In the most convincing of these, inhibitors of ADPRT were shown to block the differentiation of chick myoblasts in vitro11,12, and differentiation was accompanied by the appearance of single-strand breaks in DNA. We present here evidence that ADPRT activity is obligatory early in the mitogen-induced activation of human peripheral blood lymphocytes. The requirement for this enzyme coincides with a rapid (1–8 h) rejoining of single-strand breaks present in the DNA of quiescent lymphocytes. Hence, DNA breaking and rejoining, regulated by ADPRT, may be involved in a general mechanism of differentiation.
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Johnstone, A., Williams, G. Role of DNA breaks and ADP-ribosyl transferase activity in eukaryotic differentiation demonstrated in human lymphocytes. Nature 300, 368–370 (1982). https://doi.org/10.1038/300368a0
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DOI: https://doi.org/10.1038/300368a0
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