R Rowley1, E N Phillips, A L Schroeder. 1. Department of Radiation Oncology, University of Utah Medical Center, Salt Lake City 84132, USA. roy.rowley@hsc.utah.edu
Abstract
PURPOSE: To review observations of the effects of ionizing radiation on DNA synthesis in eukaryotes. CONTENT: Available information broadly falls into two categories: descriptions 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 eukaryotes, including man, suggest that the regulatory controls involved are highly conserved and may additionally function in G1 and G2 checkpoint controls. Budding yeast, fission yeast and human homologues are identified. CONCLUSIONS: The SDS checkpoint control appears to be comprised of a complex of checkpoint proteins that respond to the stalled replication complex. The replication complex is thought to signal down-regulation of the mitotic kinase, ensuring that the cell does not enter mitosis while S phase is delayed. Concomitantly, the checkpoint complex is believed to transmit a signal via two key checkpoint proteins (Rad3 and Cds1 in the fission yeast), in order to arrest further DNA synthesis initiation.
PURPOSE: To review observations of the effects of ionizing radiation on DNA synthesis in eukaryotes. CONTENT: Available information broadly falls into two categories: descriptions 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 eukaryotes, including man, suggest that the regulatory controls involved are highly conserved and may additionally function in G1 and G2 checkpoint controls. Budding yeast, fission yeast and human homologues are identified. CONCLUSIONS: The SDS checkpoint control appears to be comprised of a complex of checkpoint proteins that respond to the stalled replication complex. The replication complex is thought to signal down-regulation of the mitotic kinase, ensuring that the cell does not enter mitosis while S phase is delayed. Concomitantly, the checkpoint complex is believed to transmit a signal via two key checkpoint proteins (Rad3 and Cds1 in the fission yeast), in order to arrest further DNA synthesis initiation.
Authors: R S Maser; O K Mirzoeva; J Wells; H Olivares; B R Williams; R A Zinkel; P J Farnham; J H Petrini Journal: Mol Cell Biol Date: 2001-09 Impact factor: 4.272