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ATM

ATM. John Berry. What is ATM?. Named “ATM” for “Ataxia-telangiectasia Mutated” gene. The mutation is recessive. Ataxia-telangiectasia (or AT) is a neurodegenerative disease that is normally detected in infancy to early childhood.

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ATM

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  1. ATM John Berry

  2. What is ATM? • Named “ATM” for “Ataxia-telangiectasia Mutated” gene. The mutation is recessive. • Ataxia-telangiectasia (or AT) is a neurodegenerative disease that is normally detected in infancy to early childhood. • AT patients have shown a predisposition to Lymphoma, so ATM was suspected as a tumor suppressing gene. http://my.webmd.com/hw/health_guide_atoz/nord406.asp

  3. AT Symptoms • Symptoms: ataxia, telangiectasia, and impairing of the immune system http://my.webmd.com/hw/health_guide_atoz/nord406.asp

  4. AT Symptoms • Symptoms: ataxia, telangiectasia, and impairing of the immune system http://www.uv.es/derma/CLindex/CLlinfomas/CLmast9.jpg http://my.webmd.com/hw/health_guide_atoz/nord406.asp

  5. AT Effects • Patients are subject to sinopulmonary infections • Increased occurrence of malignant tumors. • Patients have a short life-expectancy. http://my.webmd.com/hw/health_guide_atoz/nord406.asp

  6. ATM • P(3)IK Serine-Threonine Kinase • Located in the Nucleus • Normally inactivated • Rapid activation in response to Double Strand Break (DSB) • Substrate list is not presently complete.

  7. ATM Function http://jncicancerspectrum.oupjournals.org.libproxy.lib.unc.edu/cgi/reprint/jnci;92/10/795.pdf

  8. ATM Substrateshttp://jncicancerspectrum.oupjournals.org.libproxy.lib.unc.edu/cgi/reprint/jnci;92/10/795.pdf

  9. ATM Checkpoint FunctionsShiloh, Yosef. “ATM AND RELATED PROTEIN KINASES: SAFEGUARDING GENOMEINTEGRITY.” Nature Reviews Cancer. Volume 3 March 2003 pg 155-168

  10. RepairMcKinnon, Peter J. “ATM and Ataxia telangiectasia.”EmboReports. Vol 3 (8) 2004. pg 772-776

  11. ATM knockout in Mice • ATM -/-: Lymphoma in 2-4 months • Heterozygous mice are predisposed. • Loss of Heterozygosity is required in most cases Barlow, C, et al. “Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell. 1996 Jul 12;86(1):159-71.

  12. Evidence for the Pathwayhttp://breast-cancer-research.com/content/pdf/bcr968.pdf

  13. Irradiated double heterozygous mice show the highest incidence of carcinogenesis http://breast-cancer-research.com/content/pdf/bcr968.pdf ATM +/-, p53 +/- Mice

  14. ATM mutations in Human Cancer • A-T Patients are not the main health concern, but rather carriers of A-T. • Most heterozygous individuals do not show a pre-disposition to cancer • Discovery of the dominant negative Shiloh, Yosef. “ATM AND RELATED PROTEIN KINASES: SAFEGUARDING GENOMEINTEGRITY.” Nature Reviews Cancer. Volume 3 March 2003 pg 155-168

  15. ATM Function http://jncicancerspectrum.oupjournals.org.libproxy.lib.unc.edu/cgi/reprint/jnci;92/10/795.pdf

  16. Future Directions • Despite a limited risk group, ATM is still important for research. • Damage repair is a key component of homeostasis.

  17. Any Questions?

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