Methods and compositions for interference with DNA polymerase and DNA synthesis

RNA Interference with DNA Polymerase and Synthesis

[0159]RNA can regulate many biological activities, including transcription and translation in cells. However, it was unknown whether RNA can directly affect DNA polymerization. It was discovered that RNA can directly interfere with DNA synthesis by altering DNA polymerase activity and turning DNA polymerase into deoxyribonucleoside triphosphate diphosphatase (dNTP-DPase). This example details the discovery and analysis of these effects of RNA on DNA polymerases. It was found that DNA polymerases of the A, B, C, and X families generally have similar dNTP-DPase activity. Moreover, it was observed that though extra RNA is lethal to cells, addition of dNTPs can rescue the cells. Furthermore, the dNTP-DPase competes with DNA polymerase for dNTPs. It was found that when the dNTP level in cell was relatively low, the dNTP-DPase activity shut down cellular DNA synthesis by hydrolyzing dNTPs. However, when the dNTP level in cell was relatively h