The effects of ionizing radiation on DNA synthesis in eukaryotic cells

Purpose: To review observations of the effects of ionizing radiation on DNA synthesis in eukaryotes. Content: Available information broadly Falls into two categories: descripti ons of the phenomenon, including dose-response data and analysis; and, more recently, investigations utilizing genetic approaches. The down-regulation of DNA replication in the presence of radiation-induced DNA damage appears to be an active cellular response, termed the S-phase damage-sensing (SDS) checkpoint control (Larner et al. 1997). Observations on a variety of euka ryotes, including man, suggest that the regulatory controls involved are hi ghly conserved and may additionally function in G(1) and G(2) checkpoint co ntrols. Budding yeast, fission yeast and human homologues are identified. Conclusions: The SDS checkpoint control appears to be comprised of a comple x of checkpoint proteins that respond to the stalled replication complex. T he replication complex is thought to signal down-regulation of the mitotic kinase, ensuring that the cell does not enter mitosis while S phase is dela yed. Concomitantly, the checkpoint complex is believed to transmit a signal via two key checkpoint proteins (Rad3 and Cds1 in the fission yeast), in o rder to arrest further DNA synthesis initiation.