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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zhao, Keji Dmitrieva, Natalia I. Cui, Kairong Kitchaev, Daniil A. Burg, Maurice B. |
| Description | Author Affiliation: Dmitrieva NI ( Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. dmitrien@nhlbi.nih.gov); |
| Abstract | High concentration of NaCl increases DNA breaks both in cell culture and in vivo. The breaks remain elevated as long as NaCl concentration remains high and are rapidly repaired when the concentration is lowered. The exact nature of the breaks, and their location, has not been entirely clear, and it has not been evident how cells survive, replicate, and maintain genome integrity in environments like the renal inner medulla in which cells are constantly exposed to high NaCl concentration. Repair of the breaks after NaCl is reduced is accompanied by formation of foci containing phosphorylated H2AX (γH2AX), which occurs around DNA double-strand breaks and contributes to their repair. Here, we confirm by specific comet assay and pulsed-field electrophoresis that cells adapted to high NaCl have increased levels of double-strand breaks. Importantly, γH2AX foci that occur during repair of the breaks are nonrandomly distributed in the mouse genome. By chromatin immunoprecipitation using anti-γH2AX antibody, followed by massive parallel sequencing (ChIP-Seq), we find that during repair of double-strand breaks induced by high NaCl, γH2AX is predominantly localized to regions of the genome devoid of genes ('gene deserts'), indicating that the high NaCl-induced double-strand breaks are located there. Localization to gene deserts helps explain why the DNA breaks are less harmful than are the random breaks induced by genotoxic agents such as UV radiation, ionizing radiation, and oxidants. We propose that the universal presence of NaCl around animal cells has directly influenced the evolution of the structure of their genomes. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 51 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA Breaks, Double-Stranded DNA Drug Effects Sodium Chloride Chemistry Animals Bleomycin Pharmacology Comet Assay Genetics DNA Damage DNA Fragmentation DNA Repair Enzymes Histones Kidney Metabolism Mice Models, Genetic Oxidants Phosphorylation Radiation, Ionizing Ultraviolet Rays Research Support, N.I.H., Intramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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