It is thus hypothesized that overexpression of Cdt1 and/or Cdc6 promotes DNA re-replication, leading to genome instability and DNA damage responses. The activated checkpoints serves as an anti-tumor barrier, which induces senescence and apoptosis to eliminate cells with severe DNA lesions associated with DNA re-replication. Loss of p53 and/or other genome caretaker genes abrogated the antitumor barriers and resulted in tumorigenesis. Consistently, loss of p53 was frequently observed in the tumors with verexpressed Cdt1 and Cdc6