Poly(ADP-ribosylation) reduces the steady-state level of breaks in DNA following treatment of human cells with alkylating agents

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Abstract
Following treatment of human fibroblasts [diploid human fibroblast strain 1BR] with dimethylsulfate [DMS], more breaks persisted in DNA in cells incubated with 3-aminobenzamide [3AB], an inhibitor of ADP-ribosyltransferase [EC 2.4.99.-], than in its absence. This effect of 3AB was more pronounced in non-dividing than in dividing cells. If non-dividing cells were treated with DMS and then incubated for a few hours in the absence of 3AB, few breaks were detectable in the DNA. Subsequent addition of 3AB resulted in the reappearance of many breaks in the DNA. Continued synthesis of poly(ADP-ribose) may reduce the steady-state level of breaks during excision repair of alkylation damage. This is probably mediated by the stimulation of DNA ligase activity. Inhibition of poly(ADP-ribose) synthesis with 3AB maintains or restores a higher steady-state level of breaks.