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Model for the replication-dependent and transcription-dependent induction of DSBs by etoposide. Upon collision with the replication fork, ss-Top2αccs and ds-Top2αccs are converted into DSBs by replication run-off. Upon collision with the transcription machinery, Top2ccs are degraded by the 26S proteasome, resulting in DSBs and SSBs. Unrepaired SSBs can also be converted to DSBs by replication run-off.
