-->

| PubMed | eMedicine | OMIM | Google | Google images | Yahoo images | YouTube |

ATR

MIM.601215 3q22-q24

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.

PIKKs, ATM and mTOR (FRAP1)

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