Effect of ionizing radiation on DNA synthesis in ataxia telangiectasia cells
J. Houldsworth,Martin F. Lavin +1 more
TLDR
The effect of ionizing radiation on DNA synthesis in control and ataxia telangiectasia (AT) lymphoblastoid cell lines was determined, and a dose dependent decrease was observed in control cells, and the rate and extent of decrease increased with time after irradiation.Abstract:
The effect of ionizing radiation on DNA synthesis in control and ataxia telangiectasia (AT) lymphoblastoid cell lines was determined. A dose dependent decrease in DNA synthesis was observed in control cells, and the rate and extent of thi decrease in synthesis increased with time after irradiation. No decrease in DNA synthesis was obtained in AT cells, immediately following irradiation, at doses up to 400 rads. At longer times postirradiation, inhibition of synthesis increased but the extent of inhibition was less in AT cell than controls at all doses used. An immediate depression of DNA synthesis was evident in control cells after a radiation dose of 200 rads reaching a maximum at 90 min postirradiation. Little or no decrease in DNA synthesis was evident in AT cells up to 60 min after the same radiation dose, but a decrease occurred between 60 and 90 min after irradiation. The rate of recovery of DNA synthesis to normal levels was more rapid in AT cells than in controls.read more
Citations
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Journal ArticleDOI
A single ataxia telangiectasia gene with a product similar to pi-3 kinase
Kinneret Savitsky,Anat Bar-Shira,Shlomit Gilad,Galit Rotman,Yael Ziv,Lina Vanagaite,Danilo A. Tagle,Sara Smith,Tamar Uziel,Sharon Sfez,Maya Ashkenazi,Iris Pecker,Moshe Frydman,Reli Harnik,Sankhavaram R. Patanjali,Andrew D. Simmons,Gregory A. Clines,Adam Sartiel,Richard A. Gatti,Luciana Chessa,Ozden Sanal,Martin F. Lavin,Nicolaas G. J. Jaspers,A. Malcolm R. Taylor,Colin F. Arlett,Toru Miki,Sherman M. Weissman,Michael Lovett,Francis S. Collins,Yosef Shiloh +29 more
TL;DR: A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia was identified by positional cloning on chromosome 11q22-23 and encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control.
Journal ArticleDOI
ATR: an essential regulator of genome integrity
Karlene A. Cimprich,David Cortez +1 more
TL;DR: New insights are provided into the mechanisms that control ATR activation, which have helped to explain the overlapping but non-redundant activities of ATR and ATM in DNA-damage signalling, and have clarified the crucial functions of AtR in maintaining genome integrity.
Journal ArticleDOI
Atm-deficient mice: a paradigm of ataxia telangiectasia.
Carrolee Barlow,Shinji Hirotsune,Richard Paylor,Marek Liyanage,Michael Eckhaus,Francis J Collins,Yosef Shiloh,Jacqueline N. Crawley,Thomas Ried,Danilo A. Tagle,Anthony Wynshaw-Boris +10 more
TL;DR: Atm-disrupted mice recapitulate the ataxia telangiectasia phenotype in humans, providing a mammalian model in which to study the pathophysiology of this pleiotropic disorder.
Journal ArticleDOI
ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response.
TL;DR: A historical perspective of their discovery is provided and their established functions in sensing and responding to genotoxic stress are discussed, as well as emerging non-canonical roles and how knowledge of ATM, ATR, and DNA-PK is being translated to benefit human health.
Journal ArticleDOI
Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer
TL;DR: First described over 80 years ago, ataxia-telangiectasia (A-T) is a paradigm for cancer predisposition and neurodegenerative disorders and has a central role in the understanding of the DNA-damage response, signal transduction and cell-cycle control.
References
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Journal ArticleDOI
Ataxia telangiectasia: a human mutation with abnormal radiation sensitivity
A. M. R. Taylor,D. G. Harnden,Colin F. Arlett,Susan A. Harcourt,Alan R. Lehmann,S. Stevens,Bryn A. Bridges +6 more
TL;DR: Cell survival experiments are reported which indicate that the clinically observed enhanced sensitivity of AT patients to ionising radiation is manifest at the cellular level.
Journal ArticleDOI
The native, denatured and renatured states of deoxyribonucleic acid
Joseph Eigner,Paul Doty +1 more
TL;DR: New and published data are analyzed to show that light-scattering determinations of molecular weight are uniformly reliable only below 3 million, and that the value of the Scheraga-Mandelkern constant β evidently remains very close to 2·4 × 10 6 throughout the molecular weight range of 200,000 to 200 million.
Journal ArticleDOI
Incorporation of 3H-uridine and 3H-uracil into RNA: a simple technique for the detection of mycoplasma contamination of cultured cells.
Edward L. Schneider,Edward L. Schneider,Eric J. Stanbridge,Eric J. Stanbridge,C.J. Epstein,C.J. Epstein +5 more
TL;DR: In this article, a simple technique for the detection of mycoplasma contamination of cultured cells was proposed, where parallel cell cultures were incubated 18 h with 3H-uridine or 3Huracil and the ratio of the specific activities of 3H -uridine labeled RNA to 3HURACil labeled RNA ( UdR U ) was determined.
Journal ArticleDOI
Evidence that xeroderma pigmentosum cells do not perform the first step in the repair of ultraviolet damage to their dna
TL;DR: Measurements of ultraviolet-induced pyrimidine dimers in cellular DNA show that normal diploid human skin fibroblasts excise up to 70 per cent of the dimer in 24 hours, but that fibro Blasts derived from the individual with XP excise less than 20 per cent in 48 hours.
Journal ArticleDOI
Defective excision repair of γ-ray-damaged DNA in human (ataxia telangiectasia) fibroblasts
TL;DR: Direct biochemical evidence is provided that diploid strains from AT donors are indeed impaired in DNA repair; in particular, these cell lines possess an enzymatic defect in an excision-type repair process operating on γ-modified nitrogenous base residues.
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A single ataxia telangiectasia gene with a product similar to pi-3 kinase
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