Consequences of the depletion of cellular deoxynucleoside triphosphate pools on the excision-repair process in cultured human fibroblasts.

DNA excision repair requires the insertion of bases into gaps in the DNA which arise during the removal of damaged sites from the chromatin. The number of bases required is dependent on the amount of damage and the patch size of repair in response to the particular type of damage. In cells in which the ability to synthesize deoxynucleoside triphosphates (dNTPs) has been compromised, repair cannot proceed to completion following doses of DNA-damaging agents which induce repair that requires greater than the steady-state level of dNTPs. Repair is thus not equally sensitive to depletion of dNTPs when measured in rapidly cycling cells with relatively high dNTP pools or in non-cycling cells with significantly smaller pools. Critical depletion of dNTPs results in the production of long-lived DNA strand breaks at repairing sites and reduction in the number of sites initiating repair. On the other hand, elevation of dNTP pools to 10-50-fold normal levels did not inhibit repair. This indicates that dNTP pool depletion but not general pool-imbalance affects DNA excision repair.