The nature of the signal triggering error-prone DNA repair function in mammalian cells was studied from two notions: 1) Does the inducing signal result from the direct hitting the cellular targets by DNA-damaging agents? 2) Is inhibition of DNA replication a prerequisite condition for the triggering effect? Thus, the ultraviolet (UV) -irradiated exogenous DNAs were introduced into human and rat cells by transfection. The results showed that this transfection was able to induce the error-prone repair as efficient as direct UV-irradiation to cells. Moreever, the two inductory treatments expressed similar kinetics and dose-responses. No matter whether the introduced DNAs initiated replication, they exhibited the inductory activity. Therefore, it can be considered that DNA lesions itself, not the direct interaction of DNA-damaging agents with specific cellular targets, serve as a triggering signal for the inductory process. Inhibition of DNA replication is not a prerequisite for the inductory signal.