Abstract
Cancer predisposition in approximately 60% of Li-Fraumeni Syndrome (LFS) families is associated with germline mutation of the TP53 gene. The p53 protein has been shown to mediate G1 arrest following DNA damage. We have investigated gamma-irradiation-induced transient and permanent G1 arrest in normal and LFS fibroblasts. The duration of transient G1 arrest varied between strains, but there was no difference in the range between normal (2-12 h) and LFS (1-13 h) cells. However, the extent of permanent G1 arrest was greatly reduced in LFS fibroblasts (mean 33+/-8% of the cell population) compared with normals (mean 67+/-9%) and correlated with their increased radiation survival (r=0.97, P<0.001). This phenotype was observed in LFS fibroblasts both with (seven cases) and without (two cases) TP53 mutation. Parallel studies with fibroblasts derived from cancer-prone, p53-deficient mice revealed no radiation-induced G1 cell cycle arrest in p53 null (-/-) cells. The p53 +/- cells were comparable to the wt p53 cells in transient G1 arrest capacity, but showed a diminished permanent G1 arrest. These data clearly implicate p53 function in permanent G1 arrest. The reduced capacity for DNA damage-induced, permanent G1 arrest in LFS may contribute significantly to cancer predisposition in this familial syndrome.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
