Cell cycle checkpoint control protein RAD9A is a protein that in humans is encoded by the RAD9A gene.Rad9 has been shown to induce G2 arrest in the cell cycle in response to DNA damage in yeast cells. Rad9 was originally found in budding yeast cells but a human homolog has also been found and studies have suggested that the molecular mechanisms of the S and G2 checkpoints are conserved in eukaryotes. Thus, what is found in yeast cells are likely to be similar in human cells. Function This gene product is highly similar to S. pombe rad9, a cell cycle checkpoint protein required for cell cycle arrest and DNA damage repair in response to DNA damage. This protein is found to possess 3' to 5' exonuclease activity, which may contribute to its role in sensing and repairing DNA damage. It forms a checkpoint protein complex with Rad1 and Hus1. This is also known as the Rad9-Rad1-Hus1 or 9-1-1 complex. This complex is recruited by checkpoint protein Rad17 to the sites of DNA damage, which is thought to be important for triggering the checkpoint-signaling cascade. Use of alternative polyA sites has been noted for this gene. This complex plays a role in DNA base excision repair. Hus1 binds and stimulates MYH DNA glycosylase which stimulates base excision repair. Rad9 binds with the strongest affinity to DNA which attaches the complex to damaged DNA. Rad1 recruits other base excision factors. Previous research has suggested that Rad9 is not necessary to repair DNA, but it does not mean it can still play a role in DNA damage repair. If Rad9 is mutated there may be other pathways or mechanisms in DNA repair that can compensate for a loss of function. Role in cell cycle DNA damage can occur as a result of a wide range of environmental and internal stressors, reactive oxygen species, radiation, and exposure to carcinogens, to name a few. In these events, specialized protein kinases ATR and ATM recognize damaged DNA and recruit various proteins to the impaired sites. As a result, ATR and ATM recruit various proteins to the damage site to stop the progression of the cell cycle before division. First, the 9-1-1 complex is recruited andactivated by ATR through phosphorylation and forms rings at the damage site. The 9-1-1 complex requires Rad17-RFC, which is independently recruited to the damage site as a cofactor, in order to bind