MCB 4010 Lecture Notes - Lecture 19: Rous Sarcoma Virus, Avian Sarcoma Leukosis Virus, Renato Dulbecco
16 Apr 2017
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Document Summary
Cells from normal tissue have a limited proliferation capacity. Normal diploid cells have a finite replicative lifespan (become senescent) Doubling potential related to age of donor. Hayflick limit (replicative lifespan) corresponds to lifespan of the organism (cells from mice have a lower replicative lifespan than do cells of a tortoise) Two barriers to immortality result from telomere shortening. Telomerase maintains ends of chromosomes: eroded at each cell division because dna polymerase requires an rna template. In late passage cells telomerase shortening reaches critical level causing p53 activation. Increased expression of cdkis halts cell cycle progression (cells remain viable) Cells escape senescence by inactivation of p53 and escape crisis by expression of telomerase. 3t3 fibroblast cells: established in 1962 by george todaro and howard green from. Swiss mouse embryo tissue: spontaneously immortalized after ~ 30 passages, p16 loss of function mutation, express telomerase. Have acquired multiple mutations in proto-oncogenes and tumor suppressor genes.
