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In cancer cells, loss of G1/S control is often accompanied by p53 pathway inactivation, the latter usually rationalized as a necessity for suppressing cell cycle arrest and apoptosis. However, we found an unanticipated effect of p53 loss in mouse and human G1-checkpoint-deficient cells: reduction of DNA damage. We show that abrogation of the G1/S-checkpoint allowed cells to enter S-phase under growth-restricting conditions at the expense of severe replication stress manifesting as decelerated DNA replication, reduced origin firing and accumulation of DNA double-strand breaks. In this system, loss of p53 allowed mitogen-independent proliferation, not by suppressing apoptosis, but rather by restoring origin firing and reducing DNA breakage. Loss of G1/S control also caused DNA damage and activation of p53 in an in vivo retinoblastoma model. Moreover, in a teratoma model, loss of p53 reduced DNA breakage. Thus, loss of p53 may promote growth of incipient cancer cells by reducing replication-stress-induced DNA damage.
Pubmed ID: 30322449 RIS Download
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View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name NU/J from IMSR.
View all literature mentionsThis monoclonal targets Trp53 monoclonal antibody clone IMX25
View all literature mentionsThis unknown targets Raised against a peptide mapping at the carboxy terminus of human p21
View all literature mentionsThis monoclonal targets Bcl-2 (100)
View all literature mentionsThis polyclonal targets CCND1
View all literature mentionsThis polyclonal targets Chk1, Phospho (S317)
View all literature mentionsThis monoclonal targets Human p130 Cas
View all literature mentionsThis monoclonal targets Chemical BrdU
View all literature mentionsThis polyclonal targets ACTG1, ACTC1, ACTA1, ACTA2, ACTG2, ACTB
View all literature mentionsThis monoclonal targets Chk1 (G-4)
View all literature mentionsThis monoclonal targets p53
View all literature mentionsCell line hTERT-RPE1 is a Telomerase immortalized cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Chemical BrdU
View all literature mentionsThis unknown targets Raised against a peptide mapping at the carboxy terminus of human p21
View all literature mentionsThis monoclonal targets Trp53 monoclonal antibody clone IMX25
View all literature mentionsThis polyclonal targets CCND1
View all literature mentionsThis monoclonal targets Bcl-2 (100)
View all literature mentionsThis monoclonal targets Human p130 Cas
View all literature mentionsThis monoclonal targets p53
View all literature mentionsThis monoclonal targets Chk1 (G-4)
View all literature mentionsThis polyclonal targets Chk1, Phospho (S317)
View all literature mentionsThis polyclonal targets ACTG1, ACTC1, ACTA1, ACTA2, ACTG2, ACTB
View all literature mentionsCell line hTERT-RPE1 is a Telomerase immortalized cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Bcl-2 (100)
View all literature mentionsThis monoclonal targets p53
View all literature mentionsThis polyclonal targets CCND1
View all literature mentionsThis monoclonal targets Human p130 Cas
View all literature mentionsThis unknown targets Raised against a peptide mapping at the carboxy terminus of human p21
View all literature mentionsThis monoclonal targets Trp53 monoclonal antibody clone IMX25
View all literature mentionsThis monoclonal targets Chk1 (G-4)
View all literature mentionsThis polyclonal targets Chk1, Phospho (S317)
View all literature mentionsThis polyclonal targets ACTG1, ACTC1, ACTA1, ACTA2, ACTG2, ACTB
View all literature mentionsThis monoclonal targets Chemical BrdU
View all literature mentionsCell line hTERT-RPE1 is a Telomerase immortalized cell line with a species of origin Homo sapiens (Human)
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