DNA strand breaks and ADP-ribosyl transferase activation during cell differentiation.

TLDR: An obligatory involvement of ADPRT activity in the differentiation of muscle cells is reported and the appearance during cytodifferentiation of single-strand DNA breaks is described which is not due to a general deficiency in DNA repair.

Abstract: The nuclear enzyme ADP-ribosyl transferase (ADPRT) catalyses the formation of poly(ADP-ribose)-modified chromatin proteins from NAD+ (refs 1–5) and is entirely dependent on DNA6 containing nicks7–11. Nuclear ADPRT activity is required for efficient DNA excision repair12,13, probably because it regulates DNA ligase activity14. Indirect evidence has suggested that ADPRT activity may also be involved in control of gene expression and cell differentiation15–21. We report here an obligatory involvement of ADPRT activity in the differentiation of muscle cells. Inhibitors of ADPRT activity reversibly inhibit both fusion of myoblasts to form multi-nucleate muscle fibres and the differentiation-specific increase in creatine phos-phokinase (CPK) activity. These two markers of differentiation can also be reversibly inhibited by depriving the cells of nicotinamide and thus lowering their cellular NAD content. Specific gene expression sometimes requires gene rearrangements or DNA transposition; this implies that DNA strand-breaking and rejoining might be involved in gene expression. We also describe the appearance during cytodifferentiation of single-strand DNA breaks which are not due to a general deficiency in DNA repair.