Quiescent murine cells lack global genomic repair but are proficient in transcription-coupled repair

Abstract

The majority of the cells in the body, including stem cells, exist in a quiescent state, so it is in quiescent cells where most DNA damage occurs. It has been uncertain whether or not this damage is repaired or fixed into mutations during quiescence or if proliferation is required for both. Prior to the development of transgenic mice, it was difficult to distinguish between these two possibilities, as cells had to proliferate to form colonies before mutations could be detected. Transgenes, however, can be shuttled out of quiescent mouse cells directly, and the level of DNA damage and mutation can be measured. Such measurements show that both mutation and repair are absent at a non-transcribed transgene in quiescent cells, although both are initiated when these cells are induced to proliferate. Conversely, the repair of transcriptionally active genes proceeds independently of proliferation in the same cells, as shown by the differential survival of wild-type and XPA-/- cells. We infer from these results that global genomic DNA repair (GGR) is not active during cellular quiescence but that transcription-coupled repair (TCR) is, suggesting that GGR is restricted to S, whereas TCR remains active throughout the cell cycle.