Ataxia telangiectasia and Rad3-related (ATR) protein is a kinase that regulates a DNA damage-response pathway.
Pathology
ATR is mutated in ATR-Seckel syndrome (ATR-SS), a disorder characterized by severe microcephaly and growth delay.
Impaired ATR signaling is also observed in cell lines from additional disorders characterized by microcephaly and growth delay, including non-ATR-SS, Nijmegen breakage syndrome, and MCPH1 (microcephaly, primary autosomal recessive, 1)-dependent primary microcephaly.
ATR signaling is a pathway unusually sensitive to haploinsufficiency.
Phosphatidylinositol 3-kinase (PIK3) activity is implicated in diverse cellular responses triggered by mammalian cell surface receptors.
Members of the phosphatidylinositol kinase-related kinase (PIKK) family are high molecular mass kinases involved in cell cycle progression, DNA recombination, and the detection of DNA damage, as ATM or FRAP1. . The ATM protein is a member of the phosphatidylinositol-3 kinase (MIM.601232) family of proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair and/or cell cycle control. The human ATM gene (MIM.607585) is defective in cells of patients with ataxia-telangiectasia (MIM.208900). ATM is involved in detection and response of cells to damaged DNA, is a member of this family.
Another member is FRAP1 (or mTOR) (MIM.601231), which is involved in a rapamycin-sensitive pathway leading to G1 cell cycle progression.
References
O’Driscoll M, Dobyns WB, van Hagen JM, Jeggo PA. Cellular and clinical impact of haploinsufficiency for genes involved in ATR signaling. Am J Hum Genet. 2007 Jul;81(1):77-86. PMID: 17564965