This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Morgan, S. E. Articles by Kastan, M. B. Search for Related Content PubMed PubMed Citation Articles by Morgan, S. E. Articles by Kastan, M. B.

 Previous Article  |  Next Article 

Mol. Cell. Biol., 04 1997, 2020-2029, Vol 17, No. 4
Copyright © 1997, American Society for Microbiology

Fragments of ATM which have dominant-negative or complementing activity

SE Morgan, C Lovly, TK Pandita, Y Shiloh and MB Kastan
The Johns Hopkins Oncology Center, Baltimore, Maryland 21205, USA.

The ATM protein has been implicated in pathways controlling cell cycle checkpoints, radiosensitivity, genetic instability, and aging. Expression of ATM fragments containing a leucine zipper motif in a human tumor cell line abrogated the S-phase checkpoint after ionizing irradiation and enhanced radiosensitivity and chromosomal breakage. These fragments did not abrogate irradiation-induced G1 or G2 checkpoints, suggesting that cell cycle checkpoint defects alone cannot account for chromosomal instability in ataxia telangiectasia (AT) cells. Expression of the carboxy-terminal portion of ATM, which contains the PI-3 kinase domain, complemented radiosensitivity and the S-phase checkpoint and reduced chromosomal breakage after irradiation in AT cells. These observations suggest that ATM function is dependent on interactions with itself or other proteins through the leucine zipper region and that the PI-3 kinase domain contains much of the significant activity of ATM.

This article has been cited by other articles:

• Kastan, M. B. (2008). DNA Damage Responses: Mechanisms and Roles in Human Disease: 2007 G.H.A. Clowes Memorial Award Lecture. Mol Cancer Res 6: 517-524 [Abstract] [Full Text]  
• Olson, E., Nievera, C. J., Liu, E., Lee, A. Y.-L., Chen, L., Wu, X. (2007). The Mre11 Complex Mediates the S-Phase Checkpoint through an Interaction with Replication Protein A. Mol. Cell. Biol. 27: 6053-6067 [Abstract] [Full Text]  
• Pylkas, K., Tommiska, J., Syrjakoski, K., Kere, J., Gatei, M., Waddell, N., Allinen, M., Karppinen, S.-M., Rapakko, K., Kaariainen, H., Aittomaki, K., Blomqvist, C., Mustonen, A., Holli, K., Khanna, K. K., Kallioniemi, O.-P., Nevanlinna, H., Winqvist, R. (2007). Evaluation of the role of Finnish ataxia-telangiectasia mutations in hereditary predisposition to breast cancer. Carcinogenesis 28: 1040-1045 [Abstract] [Full Text]  
• Gastwirt, R. F., Slavin, D. A., McAndrew, C. W., Donoghue, D. J. (2006). Spy1 Expression Prevents Normal Cellular Responses to DNA Damage: INHIBITION OF APOPTOSIS AND CHECKPOINT ACTIVATION. J. Biol. Chem. 281: 35425-35435 [Abstract] [Full Text]  
• Ho, G. P. H., Margossian, S., Taniguchi, T., D'Andrea, A. D. (2006). Phosphorylation of FANCD2 on Two Novel Sites Is Required for Mitomycin C Resistance.. Mol. Cell. Biol. 26: 7005-7015 [Abstract] [Full Text]  
• You, Z., Chahwan, C., Bailis, J., Hunter, T., Russell, P. (2005). ATM Activation and Its Recruitment to Damaged DNA Require Binding to the C Terminus of Nbs1. Mol. Cell. Biol. 25: 5363-5379 [Abstract] [Full Text]  
• Truman, J.-P., Gueven, N., Lavin, M., Leibel, S., Kolesnick, R., Fuks, Z., Haimovitz-Friedman, A. (2005). Down-regulation of ATM Protein Sensitizes Human Prostate Cancer Cells to Radiation-induced Apoptosis. J. Biol. Chem. 280: 23262-23272 [Abstract] [Full Text]  
• Gupta, A., Sharma, G. G., Young, C. S. H., Agarwal, M., Smith, E. R., Paull, T. T., Lucchesi, J. C., Khanna, K. K., Ludwig, T., Pandita, T. K. (2005). Involvement of Human MOF in ATM Function. Mol. Cell. Biol. 25: 5292-5305 [Abstract] [Full Text]  
• Viniegra, J. G., Martinez, N., Modirassari, P., Losa, J. H., Cobo, C. P., Lobo, V. J. S.-A., Luquero, C. I. A., Alvarez-Vallina, L., Ramon y Cajal, S., Rojas, J. M., Sanchez-Prieto, R. (2005). Full Activation of PKB/Akt in Response to Insulin or Ionizing Radiation Is Mediated through ATM. J. Biol. Chem. 280: 4029-4036 [Abstract] [Full Text]  
• Wang, X., Andreassen, P. R., D'Andrea, A. D. (2004). Functional Interaction of Monoubiquitinated FANCD2 and BRCA2/FANCD1 in Chromatin. Mol. Cell. Biol. 24: 5850-5862 [Abstract] [Full Text]  
• Singhi, A. D., Kondratov, R. V., Neznanov, N., Chernov, M. V., Gudkov, A. V. (2004). Selection-subtraction approach (SSA): A universal genetic screening technique that enables negative selection. Proc. Natl. Acad. Sci. USA 101: 9327-9332 [Abstract] [Full Text]  
• Buchmann, A. M., Skaar, J. R., DeCaprio, J. A. (2004). Activation of a DNA Damage Checkpoint Response in a TAF1-Defective Cell Line. Mol. Cell. Biol. 24: 5332-5339 [Abstract] [Full Text]  
• Kitagawa, R., Bakkenist, C. J., McKinnon, P. J., Kastan, M. B. (2004). Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev. 18: 1423-1438 [Abstract] [Full Text]  
• Golding, S. E., Rosenberg, E., Khalil, A., McEwen, A., Holmes, M., Neill, S., Povirk, L. F., Valerie, K. (2004). Double Strand Break Repair by Homologous Recombination Is Regulated by Cell Cycle-independent Signaling via ATM in Human Glioma Cells. J. Biol. Chem. 279: 15402-15410 [Abstract] [Full Text]  
• Wang, Y., Qin, J. (2003). MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation. Proc. Natl. Acad. Sci. USA 100: 15387-15392 [Abstract] [Full Text]  
• Sharma, G. G., Hwang, K.-k., Pandita, R. K., Gupta, A., Dhar, S., Parenteau, J., Agarwal, M., Worman, H. J., Wellinger, R. J., Pandita, T. K. (2003). Human Heterochromatin Protein 1 Isoforms HP1Hs{alpha} and HP1Hs{beta} Interfere with hTERT-Telomere Interactions and Correlate with Changes in Cell Growth and Response to Ionizing Radiation. Mol. Cell. Biol. 23: 8363-8376 [Abstract] [Full Text]  
• Lee, J. H., Xu, B., Lee, C.-H., Ahn, J.-Y., Song, M. S., Lee, H., Canman, C. E., Lee, J.-S., Kastan, M. B., Lim, D.-S. (2003). Distinct Functions of Nijmegen Breakage Syndrome in Ataxia Telangiectasia Mutated-Dependent Responses to DNA Damage. Mol Cancer Res 1: 674-681 [Abstract] [Full Text]  
• Ju, R., Muller, M. T. (2003). Histone Deacetylase Inhibitors Activate p21WAF1 Expression via ATM. Cancer Res. 63: 2891-2897 [Abstract] [Full Text]  
• Laurencon, A., Purdy, A., Sekelsky, J., Hawley, R. S., Su, T. T. (2003). Phenotypic Analysis of Separation-of-Function Alleles of MEI-41, Drosophila ATM/ATR. Genetics 164: 589-601 [Abstract] [Full Text]  
• Zhao, S., Renthal, W., Lee, E. Y.-H. P. (2002). Functional analysis of FHA and BRCT domains of NBS1 in chromatin association and DNA damage responses. Nucleic Acids Res 30: 4815-4822 [Abstract] [Full Text]  
• Wang, X., Li, G. C., Iliakis, G., Wang, Y. (2002). Ku Affects the CHK1-dependent G2 Checkpoint after Ionizing Radiation. Cancer Res. 62: 6031-6034 [Abstract] [Full Text]  
• Hannan, M. A., Hellani, A., Al-Khodairy, F. M., Kunhi, M., Siddiqui, Y., Al-Yussef, N., Pangue-Cruz, N., Siewertsen, M., Al-Ahdal, M. N., Aboussekhra, A. (2002). Deficiency in the repair of UV-induced DNA damage in human skin fibroblasts compromised for the ATM gene. Carcinogenesis 23: 1617-1624 [Abstract] [Full Text]  
• Xu, B., O'Donnell, A. H., Kim, S.-T., Kastan, M. B. (2002). Phosphorylation of Serine 1387 in Brca1 Is Specifically Required for the Atm-mediated S-Phase Checkpoint after Ionizing Irradiation. Cancer Res. 62: 4588-4591 [Abstract] [Full Text]  
• Yazdi, P. T., Wang, Y., Zhao, S., Patel, N., Lee, E. Y.-H.P., Qin, J. (2002). SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. Genes Dev. 16: 571-582 [Abstract] [Full Text]  
• Kishi, S., Lu, K. P. (2002). A Critical Role for Pin2/TRF1 in ATM-dependent Regulation. INHIBITION OF Pin2/TRF1 FUNCTION COMPLEMENTS TELOMERE SHORTENING, RADIOSENSITIVITY, AND THE G2/M CHECKPOINT DEFECT OF ATAXIA-TELANGIECTASIA CELLS. J. Biol. Chem. 277: 7420-7429 [Abstract] [Full Text]  
• Xu, B., Kim, S.-T., Lim, D.-S., Kastan, M. B. (2002). Two Molecularly Distinct G2/M Checkpoints Are Induced by Ionizing Irradiation. Mol. Cell. Biol. 22: 1049-1059 [Abstract] [Full Text]  
• Chenevix-Trench, G., Spurdle, A. B., Gatei, M., Kelly, H., Marsh, A., Chen, X., Donn, K., Cummings, M., Nyholt, D., Jenkins, M. A., Scott, C., Pupo, G. M., Dork, T., Bendix, R., Kirk, J., Tucker, K., McCredie, M. R. E., Hopper, J. L., Sambrook, J., Mann, G. J., Khanna, K. K. (2002). Dominant Negative ATM Mutations in Breast Cancer Families. JNCI J Natl Cancer Inst 94: 205-215 [Abstract] [Full Text]  
• Spring, K., Cross, S., Li, C., Watters, D., Ben-Senior, L., Waring, P., Ahangari, F., Lu, S.-l., Chen, P., Misko, I., Paterson, C., Kay, G., Smorodinsky, N. I., Shiloh, Y., Lavin, M. F. (2001). Atm Knock-in Mice Harboring an In-frame Deletion Corresponding to the Human ATM 7636del9 Common Mutation Exhibit a Variant Phenotype. Cancer Res. 61: 4561-4568 [Abstract] [Full Text]  
• Xu, B., Kim, S.-T., Kastan, M. B. (2001). Involvement of Brca1 in S-Phase and G2-Phase Checkpoints after Ionizing Irradiation. Mol. Cell. Biol. 21: 3445-3450 [Abstract] [Full Text]  
• Bullock, S. K., Kaufmann, W. K., Cordeiro-Stone, M. (2001). Enhanced S phase delay and inhibition of replication of an undamaged shuttle vector in UVC-irradiated xeroderma pigmentosum variant. Carcinogenesis 22: 233-241 [Abstract] [Full Text]  
• Peretz, S., Jensen, R., Baserga, R., Glazer, P. M. (2001). ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response. Proc. Natl. Acad. Sci. USA 10.1073/pnas.041416598v1 [Abstract] [Full Text]  
• Dhar, S., Squire, J. A., Hande, M. P., Wellinger, R. J., Pandita, T. K. (2000). Inactivation of 14-3-3sigma Influences Telomere Behavior and Ionizing Radiation-Induced Chromosomal Instability. Mol. Cell. Biol. 20: 7764-7772 [Abstract] [Full Text]  
• Fritz, E., Friedl, A. A., Zwacka, R. M., Eckardt-Schupp, F., Meyn, M. S. (2000). The Yeast TEL1 Gene Partially Substitutes for Human ATM in Suppressing Hyperrecombination, Radiation-Induced Apoptosis and Telomere Shortening in A-T Cells. Mol. Biol. Cell 11: 2605-2616 [Abstract] [Full Text]  
• Johnson, M. A., Bryant, P. E., Jones, N. J. (2000). Isolation of camptothecin-sensitive Chinese hamster cell mutants: phenotypic heterogeneity within the ataxia telangiectasia-like XRCC8 (irs2) complementation group. Mutagenesis 15: 367-374 [Abstract] [Full Text]  
• Khanna, K. K. (2000). Cancer Risk and the ATM Gene: a Continuing Debate. JNCI J Natl Cancer Inst 92: 795-802 [Abstract] [Full Text]  
• Garcia, V., Salanoubat, M., Choisne, N., Tissier, A. (2000). An ATM homologue from Arabidopsis thaliana: complete genomic organisation and expression analysis. Nucleic Acids Res 28: 1692-1699 [Abstract] [Full Text]  
• Kim, S.-T., Lim, D.-S., Canman, C. E., Kastan, M. B. (1999). Substrate Specificities and Identification of Putative Substrates of ATM Kinase Family Members. J. Biol. Chem. 274: 37538-37543 [Abstract] [Full Text]  
• Smilenov, L. B., Dhar, S., Pandita, T. K. (1999). Altered Telomere Nuclear Matrix Interactions and Nucleosomal Periodicity in Ataxia Telangiectasia Cells before and after Ionizing Radiation Treatment. Mol. Cell. Biol. 19: 6963-6971 [Abstract] [Full Text]  
• Chapman, C. R., Evans, S. T., Carr, A. M., Enoch, T. (1999). Requirement of Sequences outside the Conserved Kinase Domain of Fission Yeast Rad3p for Checkpoint Control. Mol. Biol. Cell 10: 3223-3238 [Abstract] [Full Text]  
• Suzuki, K., Kodama, S., Watanabe, M. (1999). Recruitment of ATM Protein to Double Strand DNA Irradiated with Ionizing Radiation. J. Biol. Chem. 274: 25571-25575 [Abstract] [Full Text]  
• Alarcon, C. M., Heitman, J., Cardenas, M. E. (1999). Protein Kinase Activity and Identification of a Toxic Effector Domain of the Target of Rapamycin TOR Proteins in Yeast. Mol. Biol. Cell 10: 2531-2546 [Abstract] [Full Text]  
• Guo, C. Y., Wang, Y., Brautigan, D. L., Larner, J. M. (1999). Histone H1 Dephosphorylation Is Mediated through a Radiation-induced Signal Transduction Pathway Dependent on ATM. J. Biol. Chem. 274: 18715-18720 [Abstract] [Full Text]  
• Shigeta, T., Takagi, M., Delia, D., Chessa, L., Iwata, S., Kanke, Y., Asada, M., Eguchi, M., Mizutani, S. (1999). Defective Control of Apoptosis and Mitotic Spindle Checkpoint in Heterozygous Carriers of ATM Mutations. Cancer Res. 59: 2602-2607 [Abstract] [Full Text]  
• Canman, C. E., Lim, D., Cimprich, K. A., Taya, Y., Tamai, K., Sakaguchi, K., Appella, E., Kastan, M. B., Siliciano, J. D. (1998). Activation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53. Science 281: 1677-1679 [Abstract] [Full Text]  
• Gately, D. P., Hittle, J. C., Chan, G. K. T., Yen, T. J. (1998). Characterization of ATM Expression, Localization, and Associated DNA-dependent Protein Kinase Activity. Mol. Biol. Cell 9: 2361-2374 [Abstract] [Full Text]  
• Kishi, S., Zhou, X. Z., Ziv, Y., Khoo, C., Hill, D. E., Shiloh, Y., Lu, K. P. (2001). Telomeric Protein Pin2/TRF1 as an Important ATM Target in Response to Double Strand DNA Breaks. J. Biol. Chem. 276: 29282-29291 [Abstract] [Full Text]  
• Peretz, S., Jensen, R., Baserga, R., Glazer, P. M. (2001). ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response. Proc. Natl. Acad. Sci. USA 98: 1676-1681 [Abstract] [Full Text]  
• Ferguson, A. T., Evron, E., Umbricht, C. B., Pandita, T. K., Chan, T. A., Hermeking, H., Marks, J. R., Lambers, A. R., Futreal, P. A., Stampfer, M. R., Sukumar, S. (2000). High frequency of hypermethylation at the 14-3-3 sigma locus leads to gene silencing in breast cancer. Proc. Natl. Acad. Sci. USA 97: 6049-6054 [Abstract] [Full Text]