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

Eukaryotic nuclear ADP-ribosylation reactions

“…That ADPRT activity changes during normal progressive differentiation has been extensively reported (Claycomb, 1976;Ghani & Hollenberg, 1978;Farzaneh & Pearson, 1979;Porteous et al, 1979;Rickwood & Osman, 1979;Farzaneh et al, 1982;Hacham & Ben-Ishai, 1984, and others). It appears that high poly(ADP-ribose) levels and ADPRT activity are apparent during the stage of development called commitment, but that low poly(ADP-ribose) levels exist during the overt expressional phase of differentiation (Cherney et al, 1982;Porteous & Pearson, 1982;Hacham & Ben-Ishai, 1984).…”

“…It is not certain whether DNA strand breaks, or chromatin structural changes resulting in an increased availability of ADPribose acceptors, are responsible for these changes in enzyme activity. Farzaneh et al (1982) and Johnstone & Williams (1982) concluded that spontaneous DNA strand breaks are responsible for activating the ADPRT during early differentiation events in chick myeloblasts and human lymphocytes respectively. This contrasts with the observations of Hacham & Ben-Ishai (1984) and of Althaus et al (1982), who found that transient and spontaneous alterations in ADPRT activity in primary hepatocyte cultures are not causally related to DNA fragmentation.…”

Caspase 3/caspase-activated DNase promote cell differentiation by inducing DNA strand breaks

“…In addition, a recent study has suggested that glucocorticoid-mediated gene expression is dependent on the formation of a strand break in target promoter elements; the DNA damage acts to facilitate nucleosome reorganization toward an active conformation, allowing gene expression to proceed (14). Interestingly, the appearance of transient DNA strand breaks during in vitro skeletal muscle differentiation and in vivo regeneration have been documented (15)(16)(17). Although the role of DNA damage was not investigated, these studies suggested an intriguing hypothesis that the differentiation process may be dependent on controlled DNA damage events.…”

Tumor promoter phorbol-12-myristate-13-acetate induces poly(ADP)-ribosylation in fibroblasts.

“…Poly(ADP)-ribosylation (ADPR) of chromosomal proteins may represent a mechanism of regulation of gene expression by active oxygen because it is intimately related to the redox state of the cell, DNA strand breakage and chromatin conformation (Hollenberg and Ghani, 1982;Uchigata et al, 1982;Purnell et al, 1980;Mandel et al, 1982;Poirier et al, 1985). Evidence for a role of ADPR in DNA repair (Jacobson et al, 1983;Wielckens et al, 1983;Durkacz et al, 1980), cell differentiation (Althaus et al, 1982;Johnstone and Williams, 1982;Farzaneh et al, 1982) and malignant transformation (Kun et al, 1983;Borek et al, 1984) has been obtained. We now report that the potent mouse skin promoter phorbol-12-myristate-13-acetate (PMA), which produces a prooxidant state in several cell types (see Cerutti, 1985), increased poly(ADPR) levels via the intermediacy of active oxygen in mouse embryo fibroblasts C3H1OT1/2 and human fibroblasts 3229 (Singh et al, 1985a).…”