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A Novel Function for Human Rad9 Protein as a Transcriptional Activator of Gene Expression

The human Rad9 gene is evolutionarily conserved and plays important roles in several fundamental biological processes, including promotion of resistance to DNA damage, mediating cell cycle checkpoints, acting as a proapoptotic element, and maintaining genomic integrity in the presence or even in the absence of exogenous DNA damaging agents. Rad9 protein was recently found to have the capability of activating transcription of p21, a well-known p53 target gene and universal inhibitor of cyclins and CDKs. Rad9 can bind previously defined p53 consensus sequences in the promoter region of p21. Microarray gene expression screening coupled with northern analyses revealed that Rad9 activates transcription of multiple genes, a subset of which is also controlled by p53. In this review, the newly defined ability of Rad9 to transactivate p21 and other downstream target genes is discussed in terms of the activities already associated with this protein.