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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Martín, Marta Terradas, Mariona Iliakis, George Tusell, Laura Genescà, Anna |
| Description | Country affiliation: Spain Author Affiliation: Martín M ( Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain.) |
| Abstract | After irradiation, ATM defective cells accumulate unrepaired double strand breaks (DSBs) for several cell divisions. At the chromosome level, unresolved DSBs appear as chromosome breaks that can be efficiently scored by using telomeric and mFISH probes. H2AX is immediately activated by ATM in response to DNA damage and its phosphorylated form, gammaH2AX, flanks the DSB through several megabases. The gammaH2AX-labeling status of broken chromosome ends was analyzed in AT cells to check whether the DNA damage response was accurately taking place in these persistent DSBs. The results show that one quarter of the scored breaks are devoid of gammaH2AX foci in metaphase spreads from ATM-deficient cells, and this fraction is significantly higher than in normal cells (chi(2) < 0.05). Accumulation of sensor and repair proteins at damaged sites is a key event in the cellular response to DSBs, so MRE11 labeling at broken ends was also analyzed. While all gammaH2AX foci scored at visible broken ends colocalize with MRE11 foci, all gammaH2AX-unlabeled breaks are also devoid of MRE11-labeling. The present results suggest that a significant subset of the AT long-lived DSBs may persist as 'invisible' DSBs due to deficient detection by the DNA damage repair machinery. Eventually the properly signaled DSBs will be repaired while invisible breaks may indefinitely accumulate; most probably contributing to the AT cells' well known genomic instability. |
| File Format | HTM / HTML |
| ISSN | 10452257 |
| Issue Number | 9 |
| Volume Number | 48 |
| e-ISSN | 10982264 |
| Journal | Genes, Chromosomes and Cancer |
| Language | English |
| Publisher | Wiley-Liss |
| Publisher Date | 2009-09-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Molecular Biology Discipline Oncology Ataxia Telangiectasia Genetics Dna Breaks, Double-stranded Dna-binding Proteins Deficiency Protein-serine-threonine Kinases Tumor Suppressor Proteins Metabolism Ataxia Telangiectasia Mutated Proteins Cell Cycle Proteins Cell Line, Transformed Centromere Child Chromosome Aberrations Dna Repair Gamma Rays Histones Humans In Situ Hybridization, Fluorescence Microscopy, Fluorescence Signal Transduction Sister Chromatid Exchange Telomere Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Cancer Research |
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