p53 and a human premature ageing disorder.
It has been shown that enhanced levels of p53 activity contribute to reduced cancer susceptibility in mice, however longevity is compromised due to the onset of an early-ageing phenotype. The effects of enhanced levels of p53 in these in mice could therefore have implications for human premature ageing disorders. We examined the DNA damage response of p53 and its target p21(WAF1) to UV and ionising radiation in fibroblasts from patients with the premature ageing disorder Hutchinson-Gilford Progeria (HGP). We report a normal p53 response to these DNA damaging agents suggesting that, in this particular human disorder, the premature ageing phenotype does not arise from an enhanced p53 response.
O'Neill
Mary
M
Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road, UK. m.oneill@ed.ac.uk
Núñez
Fatima
F
Melton
David W
DW
D019588:Aging, Premature / Q000235:genetics / Q000503:physiopathology; D002453:Cell Cycle / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D010641:Phenotype; D011371:Progeria / Q000235:genetics / Q000503:physiopathology*; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D014466:Ultraviolet Rays
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53