Snyder R D
Merrell Dow Research Institute, Cincinnati, OH 45215.
Mutat Res. 1988 Jul-Aug;200(1-2):193-9. doi: 10.1016/0027-5107(88)90082-6.
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.
DNA切除修复需要将碱基插入到染色质中受损位点去除过程中出现的DNA缺口处。所需碱基的数量取决于损伤的程度以及针对特定类型损伤的修复补丁大小。在合成脱氧核苷三磷酸（dNTP）的能力受到损害的细胞中，在给予诱导需要高于dNTP稳态水平的修复的DNA损伤剂剂量后，修复无法完成。因此，当在具有相对较高dNTP库的快速循环细胞或具有明显较小库的非循环细胞中进行测量时，修复对dNTP消耗的敏感性并不相同。dNTP的严重消耗会导致修复位点产生长寿命的DNA链断裂，并减少起始修复的位点数量。另一方面，将dNTP库提高到正常水平的10至50倍并不会抑制修复。这表明dNTP库的消耗而非一般的库失衡会影响DNA切除修复。
