Kai Yuet/Langer/ATM Review

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ATM Review

ATM Function And Telomere Stability

Oncogene (2002) 21, 611-618
http://www.nature.com/onc/journal/v21/n4/full/1205060a.html.

Accumulation of DNA damage has been associated with the onset of senescence and predisposition to cancer. The gene responsible for ataxia telangiectasia (A-T) is ATM (ataxia-telangiectasia mutant), a master controller of cellular pathways and networks, orchestrating the responses to a specific type of DNA damage: the double strand break. Based on the homology of the human ATM gene to the TEL1, MEC1 and rad3 genes of yeast, it has now been demonstrated that mutations in ATM lead to defective telomere maintenance in mammalian cells.

A-T homozygotes have an approximately fivefold increased risk of developing leukemia or lymphoblastic lymphomas. Cells derived from A-T individuals are hypersensitive to ionizing radiation and radiomimetic drugs.

The product of the ATM gene is a ubiquitously expressed 370 kDa phosphoprotein. It contains 3056 amino acid residues, with a distinct carboxy-terminal sequence,

By activating key regulators of multiple signal transduction pathways, ATM mediates the efficient induction of a signaling network responsible for repair of the damage, and for cellular recovery and survival.

A general consensus motif has been defined for ATM as it phosphorylates a serine or threonine residue only if it is followed by glutamine (the 'SQ/TQ' motif).

ATM phosphorylates a number of nuclear proteins, including the nuclear c-Abl tyrosine kinase, the tumor suppressor protein p53, the breast cancer susceptibility gene product BRCA1, the human checkpoint kinase hCds1/chk2, and the Nijmegen Breakage Syndrome gene product NBS1

ATM kinase activates in all phases of cell cycle; ATM dysfunction results in abnormal G1, S and G2 checkpoints.

ATM-deficient cells have telomere instability; chromosome end-to-end association, also known as telomere association (TA) is a cytological manifestation of telomere instability.


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