The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species

Savitsky, Kinneret; Sfez, Sharon; Tagle, Danilo A.; Ziv, Yael; Sartiel, Adam; Collins, Francis S.; Shiloh, Yosef; Rotman, Gallt

doi:10.1093/hmg/4.11.2025

Cited by 473 publications

(283 citation statements)

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“…This is consistent with the result described previously that only p53 mutated (EJ and TCC-sup) but not p53 wild-type (Lavin and Shiloh, 1997). Mutated ATM genes in yeast, Drosophila and mammals also result in a variety of phenotypes with features similar to human AT cells (Savitsky et al, 1995). ATM deficiency leads to growth retardation, infertility and cancer-predisposition in mice (Barlow et al, 1996).…”

Section: Discussionsupporting

confidence: 91%

Differential response of normal and malignant urothelial cells to CHK1 and ATM inhibitors

2014

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Section: Discussionsupporting

confidence: 91%

Differential response of normal and malignant urothelial cells to CHK1 and ATM inhibitors

2014

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“…In mice expressing this mutant Nbs1, there was a defect in DNA damage-induced intra-S checkpoint activation in mouse (Bakkenist and Kastan, 2003;Kozlov et al, 2006). The identified domains within ATM consist of the nuclear localization signal (NLS) , the leucine zipper (LZ) (Savitsky et al, 1995b), the FRAP/ATM/TRRAP (FAT) domain (Bosotti et al, 2000), the Kinase domain (PI3-K) (Savitsky et al, 1995a), and the FAT c-terminal (FATC) domain (Bosotti et al, 2000). (b) Nbs1 is a 90 kDa protein, consisting of 754 amino acids.…”

Section: Role Of the C-terminus Of Nbs1mentioning

confidence: 99%

Activation and regulation of ATM kinase activity in response to DNA double-strand breaks

2007

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The ataxia-telangiectasia-mutated (ATM) protein kinase is rapidly and specifically activated in response to DNA double-strand breaks in eukaryotic cells. In this review, we summarize recent insights into the mechanism of ATM activation, focusing on the role of the Mre11/Rad50/Nbs1 (MRN) complex in this process. We also compare observations of the ATM activation process in different biological systems and highlight potential candidates for cellular factors that may participate in regulating ATM activity in human cells.

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“…The ATM protein is a member of an expanding family of large proteins sharing the PI 3-kinase-like domain which were identi®ed in yeast, Drosophila and mammals. These proteins are involved in maintaining genome stability and cell cycle control, and in cellular responses to damaging agents (Savitsky et al, 1995b;Zakian, 1995;Jackson, 1995;Lavin and Shiloh, 1997). Two members of this family, DNA-dependent protein kinase (Hartley et al, 1995) and FRAP (Brown et al, 1995), were shown to be protein kinases, and it is likely that most or all of these proteins share this activity (Hunter, 1995).…”

Section: Introductionmentioning

confidence: 99%

Recombinant ATM protein complements the cellular A-T phenotype

et al. 1997

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Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by neurodegeneration, immunode®ciency, cancer predisposition, genome instability and radiation sensitivity. The cellular phenotype of A-T points to defects in signal transduction pathways involved in activation of cell cycle checkpoints by free radical damage, and other pathways that mediate the transmission of speci®c mitogenic stimuli. The product of the responsible gene, ATM, belongs to a family of large proteins that contribute to maintaining genome stability and cell cycle progression in various organisms. A recombinant vector that stably expresses a full-length ATM protein is a valuable tool for its functional analysis. We constructed and cloned a recombinant, full-length open reading frame of ATM using a combination of vectors and hosts that overcame an inherent instability of this sequence. Recombinant ATM was stably expressed in insect cells using a baculovirus vector, albeit at a low level, and in human A-T cells using an episomal expression vector. An amino-terminal FLAG epitope added to the protein allowed highly speci®c detection of the recombinant molecule by immunoblotting, immunoprecipitation and immunostaining, and its isolation using immunoanity. Similar to endogenous ATM, the recombinant protein is located mainly in the nucleus, with low levels in the cytoplasm. Ectopic expression of ATM in A-T cells restored normal sensitivity to ionizing radiation and the radiomimetic drug neocarzinostatin, and a normal pattern of post-irradiation DNA synthesis, which represents an Sphase checkpoint. These observations indicate that the recombinant, epitope-tagged protein is functional. Introduction into this molecule of a known A-T missense mutation, Glu2904Gly, resulted in apparent instability of the protein and inability to complement the A-T phenotype. These ®ndings indicate that the physiological defects characteristic of A-T cells result from the absence of the ATM protein, and that this de®ciency can be corrected by ectopic expression of this protein.

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The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species

Cited by 473 publications

References 0 publications

Differential response of normal and malignant urothelial cells to CHK1 and ATM inhibitors

Differential response of normal and malignant urothelial cells to CHK1 and ATM inhibitors

Activation and regulation of ATM kinase activity in response to DNA double-strand breaks

Recombinant ATM protein complements the cellular A-T phenotype

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