title: p53 activates G₁ checkpoint following DNA damage by doxorubicin during transient mitotic arrest.
abstract: Recovery from DNA damage is critical for cell survival. The serious damage is not able to be repaired during checkpoint and finally induces cell death to prevent abnormal cell growth. In this study, we demonstrated that 8N-DNA contents are accumulated via re-replication during prolonged recovery period containing serious DNA damage in mitotic cells. During the incubation for recovery, a mitotic delay and initiation of an abnormal interphase without cytokinesis were detected. Whereas a failure of cytokinesis occurred in cells with no relation with p53/p21, re-replication is an anomalous phenomenon in the mitotic DNA damage response in p53/p21 negative cells. Cells with wild-type p53 are accumulated just prior to the initiation of DNA replication through a G₁ checkpoint after mitotic DNA damage, even though p53 does not interrupt pre-RC assembly. Finally, these cells undergo cell death by apoptosis. These data suggest that p53 activates G₁ checkpoint in response to mitotic DNA damage. Without p53, cells with mitotic DNA damage undergo re-replication leading to accumulation of damage.
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Korea.
authors.forename: Sun-Yi
authors.initials: SY
authors.lastname: Hyun
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Korea.
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D008938:Mitosis / Q000187:drug effects / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin
keywords: apoptosis; damage adaptation; mitotic DNA damage; multiploidy; p53; re-replication