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Figure 16. Cells defective in telomere replocation fail to arrest cell division at the restrictive temperature. cdc13 RAD9 cells incubated at the restrictive temperature for several hours have arrested cell division and retain viability (A) but cdc13 rad9 cells failed to arrest and die (B). Reproduced from ref 29 with permission.

The rad9 mutant exhibited a 20 fold increase in the rate of chromosome loss in the absence of any extrinsic DNA damage. An explanation for the increase in chromosome loss in checkpoint defective cells was provided by Tedís discovery that the same mutations that rendered cells insensitive to arrest of mitosis by radiation also rendered cells insensitive to arrest by defects in DNA replication. This suggested that intrinsic errors in DNA replication occurred stochastically in rare cells of the population and that the checkpoint function was needed in those cells to assure correct repair of the damage. The same checkpoint genes were later found by Mandy Paulovitch to control the rate of replication over damaged DNA (30) and by Siede, Friedberg and Friedberg to control the rate at which cells enter S phase when they experience damage in G1 (31).