rad1

rad1 is a nuclear protein encoded by the RAD1 gene in Homo sapiens. It is a part of the 9‑1‑1 (RAD9‑RAD1‑HUS1) heterotrimeric clamp that is loaded onto DNA at sites of damage or replication stress by the RFC clamp loader. The RAD1 subunit contains an N‑terminal domain that mediates complex formation and a C‑terminal domain that participates in protein–protein interactions. RAD1 is highly conserved across eukaryotes, with orthologs in yeast (Rad1p), Drosophila (Rad1), and Arabidopsis (AtRAD1).

The 9‑1‑1 complex functions primarily as a scaffold to recruit checkpoint kinases, including ATM, ATR, and CHK2, thereby activating DNA damage signaling pathways that stall the cell cycle and promote repair. RAD1 also interacts with topoisomerase II and components of the replication machinery, indicating a role in replication fork stability. Proteomic studies reveal that RAD1 can bind topoisomerase‑binding protein (TOPBP1) and the clamp loader subunit RFC1, further linking it to the regulation of DNA replication integrity.

Mutations or reduced expression of RAD1 are associated with genomic instability and increased sensitivity to ionizing radiation. In humans, inherited variants that impair RAD1 function contribute to a predisposition for cancers such as colorectal and pancreatic carcinoma, and may underlie certain radiosensitivity syndromes. Disruption of the RAD1 gene in model organisms produces embryonic lethality or developmental defects, underscoring its essential role.

The RAD1 gene resides on chromosome 9q34.1 in humans and is transcriptionally regulated by p53. Its expression is cell‑cycle–dependent, peaking during S‑phase. Bioinformatic analyses show conserved motifs required for clamp loading and ATPase activity. Largely, RAD1 remains a key component of the DNA damage checkpoint that safeguards genome integrity.