Rad9 S1260 Antibody

Cells respond to DNA damage by activating a network of signaling pathways that control cell cycle progression and DNA repair.  Cell cycle checkpoints are mechanisms that transiently delay cell cycle progression when DNA is damaged or DNA replication is incomplete. In the fission yeast Schizosaccharomyces pombe, a group of six such checkpoint control genes have been identified and include rad1+, rad3+, rad9+, rad17+, rad26+ and hus1+. Mutations in any one of these genes render cells sensitive to gamma-rays, UV light or the DNA synthesis inhibitor hydroxyurea (HU) and eliminate the ability of cells to delay entry into mitosis after treatment with these agents. All of these genes apparently link abnormal DNA structures to cell cycle control.  As for cell cycle-related genes in general, these checkpoint control genes are highly conserved throughout evolution. Human and mouse versions of several of the S.pombe genes have been isolated, providing strong evidence that checkpoint control mechanisms are also highly conserved. In mammals, these genes are thought to maintain genomic stability, especially in the presence of DNA damage. Therefore, when these genes are altered, genomic instability may occur and lead to cancer.  The biochemical activities of most of the checkpoint control gene products are not well established, although progress has been made towards learning more about their function. For example, examination of the structure of the protein encoded by human or S.pombe rad9 reveals a BH3-like domain in the N-terminal region that can bind the anti-apoptotic proteins Bcl-2 and Bcl-X_L. Furthermore, overexpression of the gene from either organism in human cells can cause apoptosis in a BH3 domain-dependent manner. Both S.pombe and human versions of the protein can bind two other checkpoint control proteins, Hus1p (HUS1p) and Rad1p (RAD1p). Human RAD9 protein binds HUS1 and RAD1 proteins at its C-terminal region, suggesting that RAD9 has at least two functional domains, one involved in apoptosis and the other in cell cycle checkpoint control.  Rad9 conveys the checkpoint signal by activating Rad53p and Chk1p; is hyperphosphorylated by Mec1p and Tel1p; and is a potential Cdc28p substrate.