Rad9

Rad9 is a DNA damage response protein found in a range of eukaryotes, including the budding yeast Saccharomyces cerevisiae and humans. In yeast, Rad9 functions as a mediator of the Mec1-Ddc2 checkpoint signaling pathway and is required for efficient activation of the downstream Rad53 kinase after DNA damage or replication stress. This promotes cell cycle arrest and facilitates DNA repair. Rad9 localizes to sites of damage and is regulated by phosphorylation, which modulates its mediator activity. Mutants lacking Rad9 show increased sensitivity to DNA damaging agents such as methyl methanesulfonate and ultraviolet light and impaired checkpoint enforcement.

Across many organisms, Rad9 is associated with the 9-1-1 DNA damage clamp, a heterotrimeric ring that recognizes damaged DNA and helps recruit and coordinate ATR/ATM signaling and repair factors. The clamp is loaded onto DNA at damaged sites by a clamp loader complex and serves as a platform for downstream effectors. In humans, RAD9 is a core subunit of the 9-1-1 clamp (Rad9-Hus1-Rad1) and participates in cell cycle arrest, DNA repair, and apoptosis signaling. It interacts with a range of repair proteins and has reported associations with p53 and BRCA1, linking damage sensing to transcriptional and repair responses.

Rad9 proteins are conserved across eukaryotes, though specific roles and interactions vary. In yeast, the primary described function is checkpoint mediation; in vertebrates, additional involvement in repair coordination and apoptosis has been documented.