ATM (ataxia telangiectasia mutated): expanding roles in the DNA damage response and cellular homeostasis.
DNA damage is one of the most acute threats to cellular homeostasis and life. The cell responds to such damage by activating a vast array of responses, ranging from DNA repair to numerous signalling pathways, which temporarily slow down the cellular life cycle while the damage is being repaired. Sophisticated relays convey the DNA damage alarm to all these systems immediately after damage infliction. Such relays must be capable of sensing the damage and rapidly creating functional contact with many signalling networks. The ataxia telangiectasia mutated (ATM) protein is a prominent example of such a relay. It responds swiftly to a critical DNA damage - the double strand break (DSB) - by phosphorylating key proteins in numerous signalling pathways. Evidence is emerging, however, that the ATM protein might also be involved in other processes related to cellular homeostasis, which are not directly associated with the damage response. ATM is the protein product of the gene mutated in the multisystem disorder ataxia-telangiectasia (AT), which is characterized by neuronal degeneration, immunodeficiency, chromosomal instability and cancer predisposition. The AT phenotype and the functions of the ATM protein revealed to date demonstrate the exceptionally multifaceted nature of this protein.
Shiloh
Y
Y
The David and Inez Myers Laboratory for Genetic Research, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. yossih@post.tau.ac.il
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004249:DNA Damage; D004268:DNA-Binding Proteins; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology*; D011995:Recombination, Genetic; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006133:Growth Substances; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases