Role of RAD9-dependent cell-cycle checkpoints in the adaptive response to ionizing radiation in yeast, Saccharomyces cerevisiae.
OBJECTIVE
To determine whether yeast cells (Saccharomyces cerevisiae) defective in damage-inducible cell-cycle arrest can invoke an adaptive response and become resistant to normally lethal doses of ionizing radiation.


METHODS
Wild-type yeast cells, cells defective for DNA-damage-responsive G1 and G2 cell-cycle arrest (rad9delta), and cells defective for recombinational repair of DNA damage (rad50, 51, 52) were subjected to adapting treatments of heat or radiation and subsequently exposed to normally lethal doses of radiation. Survival, as measured by colony-forming ability, was compared with non-adapted, control cells.


RESULTS
Wild-type and rad9delta cells became more resistant to potentially lethal doses of radiation after exposure to conditions that are known to elicit the adaptive response. Further, the relative magnitude of resistance developed by the normal, wild-type and rad9delta yeast cells was similar, with a dose modifying factor (at D1) for radiation-induced radiation resistance of 1.3 for both strains. Dose modifying factors (at D1) for heat-induced radiation resistance were 1.7 and 1.6 for wild-type and rad9delta cells, respectively. In contrast, none of the recombinational repair-defective cells exhibited radiation resistance after an adapting treatment.


CONCLUSIONS
The ability of yeast cells to arrest in cell-cycle gap phases did not appear to contribute significantly to radiation resistance induced by radiation or heat. Instead, it is suggested that the adaptive response was due mainly to the existence and enhancement of cellular recombinational repair capacity, which was sufficient to repair any DNA damage without the requirement of a detectable cell-cycle delay.
Dolling
J A
JA
Radiation Biology and Health Physics Branch, AECL, Chalk River, Ontario, Canada. dollingj@aecl.ca
Boreham
D R
DR
Bahen
M E
ME
Mitchel
R E
RE
D002453:Cell Cycle / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D003037:Cobalt Radioisotopes; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006358:Hot Temperature; D009154:Mutation; D011836:Radiation Tolerance; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000528:radiation effects*; D013696:Temperature; D013997:Time Factors; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D003037:Cobalt Radioisotopes; C069930:rad9 protein