Critical DNA damage and mammalian cell reproduction

Synchronous Chinese hamster cells accumulated 125I-induced DNA damage in the G 2 + M† period at 4 °C. The position of the 125I within the nuclear DNA was varied by incorporating [ 125I]iododeoxyuridine at various times during the previous DNA replication period. When the initial cell inactivation efficiency was compared for damage accumulated in various regions of nuclear DNA, it was found that the efficiency of inactivation was least in early replicating DNA, and that it gradually increased, reaching a maximum during the fourth and fifth hours of the six-hour DNA replication period. Because the DNA that replicated during this maximum corresponds to that DNA which later forms centromeric and near-centromeric regions of the chromosomes, damage in centromeric region DNA may be critical in causing mammalian cell inactivation.