The RAD9 Gene Controls the Cell Cycle Response to DNA Damage in Saccharomyces cerevisiae

Abstract

Cell division is arrested in many organisms in response to DNA damage. Examinations of the genetic basis for this response in the yeast Saccharomyces cerevisiae indicate that the RAD9 gene product is essential for arrest of cell division induced by DNA damage. Wild-type haploid cells irradiated with x-rays either arrest or delay cell division in the G2 phase of the cell cycle. Irradiated G1 and M phase haploid cells arrest irreversibly in G2 and die, whereas irradiated G2 phase haploid cells delay in G2 for a time proportional to the extent of damage before resuming cell division. In contrast, irradiated rad9 cells in any phase of the cycle do not delay cell division in G2, but continue to divide for several generations and die. However, efficient DNA repair can occur in irradiated rad9 cells if irradiated cells are blocked for several hours in G2 by treatment with a microtubule poison. The RAD9-dependent response detects potentially lethal DNA damage and causes arrest of cells in G2 until such damage is repaired.

BRCA1 gene in breast cancer

“…However, the authors provide evidence that this protein is phosphorylated; and nuclear localization may occur by interaction with another nucleoprotein. The mechanism by which BRCA1 regulates G2/M progression is unclear, but it is noteworthy that the truncated BRCA1 protein contains domains that interact with the RNA polymerase II holoenzyme (Scully et al, 1997a;Anderson et al, 1998;Schlegel et al, 2000a;Chiba and Parvin, 2002) as well as a region homologous to Rad9, a protein involved in the G2 damage-responsive cell cycle checkpoint (Weinert and Hartwell, 1988;Hirai and Wang, 2002;Yoshida et al, 2002). Roles for BRCA1 in several DNA damageresponsive checkpoints (including G2/M) have been established and are discussed (see ''Caretaker Role: Maintenance of Genomic Integrity'').…”

Cloning of rat GADD45 gene and induction analysis following ionizing radiation in vivo

“…Several enzymes are activated during the G1 and G2 phases in response to DNA damage. For example, the sulA gene, one of the RecA SOS related gene, inhibits cell growth upon DNA damage in E. coli [2], and the RAD9 gene causes cell cycle arrest at G2 following X-ray irradiation in Saccharomyces cerevisiae [3]. Thus, these cell cycle phases function as cell cycle check points [4].…”

Involvement of cell cycle progression in survival signaling through CD40 in the B-lymphocyte line WEHI-231

“…38,39 For instance, ionizing irradiation induces DNA damage, which activates DNA damage checkpoint, thereby causing cell cycle arrest. 40 The arrest allows the cells to repair DNA damage before proceeding cell cycle progression. Abrogation of checkpoint causes immature cell cycle entry, resulting in mitotic catastrophe and cell death.…”