Anti-Phospho SQ/TQ ATM/ATR Substrate antibody

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

The Phospho SQ/TQ ATM/ATR Substrate often referred to as ATM/ATR phosphosubstrate plays a mechanical role in the DNA damage response by serving as a recognition site for phosphorylation. ATM (Ataxia-telangiectasia mutated) and ATR (ATM-Rad3-related) are serine/threonine protein kinases that phosphorylate this substrate facilitating the cellular response to DNA strand breaks. Each protein has a significant mass with ATM weighing approximately 350 kDa and ATR at about 300 kDa. This substrate is expressed in various tissues particularly in those with high rates of cell division such as bone marrow and the gastrointestinal tract.

Biological function summary

The phosphorylation events on the SQ/TQ motifs by ATM and ATR signal and mediate the coordination of cell cycle checkpoints. This process ensures proper repair or apoptosis in response to genotoxic stress. As part of the broader DDR (DNA Damage Response) mechanism these phosphorylations trigger the recruitment of BRCA1 and CHK1 integrating the substrate within a complex web of protein interactions. This highlights their strategic role in maintaining the integrity of cellular DNA and genomic stability.

Pathways

The ATM/ATR phosphosubstrate is integral to the DNA damage signaling pathway and the cell cycle control pathway. ATM and ATR through the phosphorylation of this substrate enable pathways that arrest the cell cycle allowing for DNA repair or apoptosis. Key related proteins include p53 which ATM stabilizes through phosphorylation and RAD9 a checkpoint regulator that ATR activates. These pathways unequivocally contribute to cellular defense mechanisms against genomic instability.

Phosphorylation of the SQ/TQ substrate by ATM and ATR links to conditions such as ataxia-telangiectasia and cancer. Mutations in the ATM gene impair the phosphorylation capability leading to ataxia-telangiectasia a disorder characterized by neurological dysfunction and cancer predisposition. Meanwhile in cancer defective ATM/ATR signaling or phosphorylation activities prompt uncontrolled cell proliferation due to inadequate DNA repair. The inactivation of downstream proteins like p53 and CHK2 often accompanies these disorders contributing further to the disease pathophysiology.