5 results on '"Nnennaya Kanu"'
Search Results
2. 1228P Integrated analysis of gene expression and chromosomal aberrations to determine the global patterns of DNA methylation heterogeneity in the TRACERx lung study
- Author
-
Olga Chervova, Miljana Tanic, Pawan Dhami, P. Van Loo, K. Chen, Nnennaya Kanu, F. Gimeno-Valiente, Elizabeth Larose Cadieux, Charles Swanton, Heli Vaikkinen, Stephan Beck, Jonas Demeulemeester, Thomas B.K. Watkins, and Andrew Feber
- Subjects
Lung ,medicine.anatomical_structure ,Oncology ,business.industry ,DNA methylation ,Gene expression ,Cancer research ,medicine ,Hematology ,business - Published
- 2020
- Full Text
- View/download PDF
3. Competition between NBS1 and ATMIN Controls ATM Signaling Pathway Choice
- Author
-
Tianyi Zhang, Nnennaya Kanu, Axel Behrens, Kay Penicud, Christopher Bruhn, Zhao-Qi Wang, and Joanna I. Loizou
- Subjects
Cell Cycle Proteins ,Ataxia Telangiectasia Mutated Proteins ,Protein Serine-Threonine Kinases ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Mice ,03 medical and health sciences ,Substrate-level phosphorylation ,0302 clinical medicine ,Animals ,Humans ,DNA Breaks, Double-Stranded ,lcsh:QH301-705.5 ,Transcription factor ,030304 developmental biology ,Genetics ,0303 health sciences ,Tumor Suppressor Proteins ,Nuclear Proteins ,Phenotype ,Mice, Mutant Strains ,Chromatin ,Cell biology ,DNA-Binding Proteins ,lcsh:Biology (General) ,Cell culture ,030220 oncology & carcinogenesis ,Alternative complement pathway ,Carrier Proteins ,Flux (metabolism) ,Signal Transduction ,Transcription Factors - Abstract
SummaryAtaxia telangiectasia mutated (ATM) protein kinase activation by DNA double-strand breaks (DSBs) requires the Mre11-Rad50-NBS1 (MRN) complex, whereas ATM interactor (ATMIN) protein is required for ATM signaling induced by changes in chromatin structure. We show here that NBS1 and ATMIN proteins compete for ATM binding and that this mechanism controls ATM function. DSB-induced ATM substrate phosphorylation was increased in atmin mutant cells. Conversely, NBS1 deficiency resulted in increased ATMIN-dependent ATM signaling. Thus, the absence of one cofactor increased flux through the alternative pathway. Notably, ATMIN deficiency rescued the cellular lethality of NBS1-deficient cells, and NBS1/ATMIN double deficiency resulted in complete abrogation of ATM signaling and profound radiosensitivity. Hence, ATMIN and NBS1 mediate all ATM signaling by DSBs, and increased ATMIN-dependent ATM signaling explains the different phenotypes of nbs1- and atm-mutant cells. Thus, the antagonism and redundancy of ATMIN and NBS1 constitute a crucial regulatory mechanism for ATM signaling and function.
- Published
- 2012
- Full Text
- View/download PDF
4. The ATM Cofactor ATMIN Protects against Oxidative Stress and Accumulation of DNA Damage in the Aging Brain
- Author
-
Elaine E. Irvine, Mariya Hristova, Gennadij Raivich, Barnaby Wong, Axel Behrens, Florian Plattner, Kay Penicud, and Nnennaya Kanu
- Subjects
Senescence ,Aging ,DNA repair ,DNA damage ,Cell Cycle Proteins ,Ataxia Telangiectasia Mutated Proteins ,Protein Serine-Threonine Kinases ,Biology ,medicine.disease_cause ,Biochemistry ,Antioxidants ,Histones ,Mice ,medicine ,Animals ,Aging brain ,Phosphorylation ,Molecular Biology ,Cells, Cultured ,Cellular Senescence ,Cerebral Cortex ,Neurons ,Tumor Suppressor Proteins ,Nuclear Proteins ,Molecular Bases of Disease ,Cell Biology ,Fibroblasts ,Embryo, Mammalian ,medicine.disease ,Mice, Mutant Strains ,Cell biology ,DNA-Binding Proteins ,Oxygen ,Oxidative Stress ,Ataxia-telangiectasia ,Embryo Loss ,Carrier Proteins ,Cell aging ,Oxidative stress ,DNA Damage ,Transcription Factors - Abstract
Progressive accumulation of DNA damage is causally involved in cellular senescence and organismal aging. The DNA damage kinase ATM plays a central role in maintaining genomic stability. ATM mutations cause the genetic disorder ataxia telangiectasia, which is primarily characterized by progressive neurodegeneration and cancer susceptibility. Although the importance of ATM function to protect against oxidative DNA damage and during aging is well described, the mechanism of ATM activation by these stimuli is not known. Here we identify ATM interactor (ATMIN) as an essential component of the ATM signaling pathway in response to oxidative stress and aging. Embryos lacking ATMIN (atmin(Δ/Δ)) died in utero and showed increased numbers of cells positive for phosphorylated histone H2aX, indicative of increased DNA damage. atmin(Δ/Δ) mouse embryonic fibroblasts accumulated DNA damage and prematurely entered senescence when cultured at atmospheric oxygen levels (20%), but this defect was rescued by addition of an antioxidant and also by culturing cells at physiological oxygen levels (3%). In response to acute oxidative stress, atmin(Δ/Δ) mouse embryonic fibroblasts showed slightly lower levels of ATM phosphorylation and reduced ATM substrate phosphorylation. Conditional deletion of ATMIN in the murine nervous system (atmin(ΔN)) resulted in reduced numbers of dopaminergic neurons, as does ATM deficiency. ATM activity was observed in old, but not in young, control mice, but aging-induced ATM signaling was impaired by ATMIN deficiency. Consequently, old atmin(ΔN) mice showed accumulation of DNA damage in the cortex accompanied by gliosis, resulting in increased mortality of aging mutant mice. These results suggest that ATMIN mediates ATM activation by oxidative stress, and thereby ATMIN protects the aging brain by preventing accumulation of DNA damage.
- Published
- 2010
- Full Text
- View/download PDF
5. Transfer of Scrapie Prion Infectivity by Cell Contact in Culture
- Author
-
Jeremy P. Brockes, Christopher J. Bostock, R. Anthony Williamson, Yutaka Imokawa, David N. Drechsel, Nnennaya Kanu, and Christopher R. Birkett
- Subjects
Cell signaling ,Cell type ,Tissue Fixation ,PrPSc Proteins ,medicine.drug_class ,Polymers ,animal diseases ,Cell ,Scrapie ,Cell Communication ,Biology ,Monoclonal antibody ,General Biochemistry, Genetics and Molecular Biology ,Microbiology ,Cell Line ,chemistry.chemical_compound ,Fixatives ,Mice ,Formaldehyde ,medicine ,Animals ,PrPC Proteins ,Methionine ,Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,Coculture Techniques ,Cell biology ,nervous system diseases ,medicine.anatomical_structure ,chemistry ,Cell culture ,General Agricultural and Biological Sciences - Abstract
Background When a cell is infected with scrapie prions, newly synthesized molecules of the prion protein PrP C are expressed at the cell surface and may subsequently be converted to the abnormal form PrP Sc . In an experimental scrapie infection of an animal, the initial innoculum of PrP Sc is cleared relatively rapidly, and the subsequent propagation of the infection depends on the ability of infected cells to convert uninfected target cells to stable production of PrP Sc . The mechanism of such cell-based infection is not understood. Results We have established a system in dissociated cell culture in which scrapie-infected mouse SMB cells are able to stably convert genetically marked target cells by coculture. After coculture and rigorous removal of SMB cells, the target cells express PrP Sc and also incorporate [ 35 S]methionine into PrP Sc . The extent of conversion was sensitive to the ratio of the two cell types, and conversion by live SMB required 2500-fold less PrP Sc than conversion by a cell-free prion preparation. The conversion activity of SMB cells is not detectable in conditioned medium and apparently depends on close proximity or contact, as evidenced by culturing the SMB and target cells on neighboring but separate surfaces. SMB cells were killed by fixation in aldehydes, followed by washing, and were found to retain significant activity at conversion of target cells. Conclusions Cell-mediated infection of target cells in this culture system is effective and requires significantly less PrP Sc than infection by a prion preparation. Several lines of evidence indicate that it depends on cell contact, in particular, the activity of aldehyde-fixed infected cells.
- Published
- 2002
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.