Mammalian cells: Damage in late replicating DNA as the most efficient cause of reproductive death

Abstract

Chinese hamster cells were synchronized by mitotic shake off, labeled in the first S period with 125IUdR, cooled to 4 °C in the G2 stage and then stored up to 4 days to accumulate damage due to 125I disintegrations in cell DNA. There was a large difference in the efficiency of induction of reproductive death when damage accumulated in the DNA, which replicated in the second half of the DNA synthesis period, was compared with damage accumulated in the DNA, which replicated in the first half of the DNA synthesis period. Damage accumulated in the late replicated DNA appears to be the most critical. This result suggests that the mammalian cell nucleus is not homogeneous with respect to the damaging events leading to reproductive death and may stress the importance for cell survival of the integrity of the late-replicating, heterochromatic DNA near the nucleus membrane.