p53-independent DNA repair and cell cycle arrest in embryonic stem cells.
The role of p53 in DNA repair and cell cycle checkpoint after ultraviolet irradiation was investigated in an embryonic stem cell line homozygous for a targeted deletion of p53. Results indicate that loss of p53 does not alter the capacity of ES cells to respond to DNA damage. Wild-type and p53-deficient cells showed similar cessation of DNA synthesis after UV damage and similar ultimate capacity to repair a transiently transfected reporter plasmid. Interestingly, in the absence of DNA damaging treatment, the transit of p53-deficient cells through S phase was slower than wild-type cells. We suggest that this may result from the absence of a p53-dependent response to endogenous DNA damage: without p53 sensing endogenous damage leading to immediate repair, such damage may persist and thus delay DNA synthesis.
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Cancer Research Campaign Laboratories, University Department of Pathology, Medical School, Edinburgh, Scotland, UK.
Bellamy
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Clarke
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Wyllie
A H
AH
Harrison
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DJ
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000502:physiology*; D004261:DNA Replication / Q000235:genetics; D005434:Flow Cytometry; D017353:Gene Deletion; D017930:Genes, Reporter / Q000235:genetics; D007399:Interphase / Q000502:physiology; D051379:Mice; D016196:S Phase / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D014466:Ultraviolet Rays / Q000009:adverse effects
D016159:Tumor Suppressor Protein p53; D015500:Chloramphenicol O-Acetyltransferase