Abstract

This is a new proposal, the intention is to investigate At, regulated apoptosis with the ultimate goal of elucidating downstream effectors of Atm signaling. The proposal is based on preliminary data indicating that specific populations of dividing cells in the Atm knockout nervous system are protected from the pro-apoptotic effects of ionizing radiation.
The aims of the application will be to identify potential physiologically relevant activators (oxidative stress, excitotoxicity, axotomy) of the Atm signaling pathway by using Atm -/- mice and neuronal cell cultures derived from these animals; to identify components of the apoptotic pathway involving Atm and the nervous system by using the Atm -/- mice as well as p53, Bcl-2 and Bax -/- mice, and cultures derived from these animals and finally, to exhaustively investigate and characterize the developing nervous system in the Atm -/- mice and to ask whether Atm is important for normal programmed cell death.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS037956-01
Application #
2705246
Study Section
Special Emphasis Panel (ZRG1-NLS-3 (01))
Program Officer
Spinella, Giovanna M
Project Start
1998-08-01
Project End
2002-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105

  Publications

Illuzzi, Jennifer L; McNeill, Daniel R; Bastian, Paul et al. (2017) Tumor-associated APE1 variant exhibits reduced complementation efficiency but does not promote cancer cell phenotypes. Environ Mol Mutagen 58:84-98
Chiang, Shih-Chieh; Meagher, Martin; Kassouf, Nick et al. (2017) Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical-induced DNA damage. Sci Adv 3:e1602506
Enriquez-Rios, Vanessa; Dumitrache, Lavinia C; Downing, Susanna M et al. (2017) DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis. J Neurosci 37:893-905
Higo, Tomoaki; Naito, Atsuhiko T; Sumida, Tomokazu et al. (2017) DNA single-strand break-induced DNA damage response causes heart failure. Nat Commun 8:15104
Canela, Andres; Maman, Yaakov; Jung, Seolkyoung et al. (2017) Genome Organization Drives Chromosome Fragility. Cell 170:507-521.e18
ElInati, Elias; Russell, Helen R; Ojarikre, Obah A et al. (2017) DNA damage response protein TOPBP1 regulates X chromosome silencing in the mammalian germ line. Proc Natl Acad Sci U S A 114:12536-12541
Hoch, Nicolas C; Hanzlikova, Hana; Rulten, Stuart L et al. (2017) XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia. Nature 541:87-91
Dumitrache, Lavinia C; McKinnon, Peter J (2017) Polynucleotide kinase-phosphatase (PNKP) mutations and neurologic disease. Mech Ageing Dev 161:121-129
McKinnon, Peter J (2017) Genome integrity and disease prevention in the nervous system. Genes Dev 31:1180-1194
Ho, Yeung; Li, Xiting; Jamison, Stephanie et al. (2016) PERK Activation Promotes Medulloblastoma Tumorigenesis by Attenuating Premalignant Granule Cell Precursor Apoptosis. Am J Pathol 186:1939-1951

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