Most cited article - PubMed ID 12941600
Nuclear and territorial topography of chromosome telomeres in human lymphocytes
This paper has been prepared to commemorate the 70th anniversary of the Institute of Biophysics of the Czech Academy of Sciences (IBP CAS), which has a long-standing tradition in researching the biological effects of ionizing radiation (IR). Radiobiology has recently gained renewed importance due to several compelling factors. The demand for a better understanding of the biological effects of both low and high doses of various types of ionizing radiation, along with improved radiation protection, is increasing-particularly in the context of critical ongoing human activities such as medical diagnostics, radiotherapy, and the operation of nuclear power plants. This demand also extends to newly emerging scenarios, including the development of hadron and FLASH radiotherapy, as well as mixed radiation field exposures related to planned manned missions to Mars. Unfortunately, there is also an urgent need to address the heightened risk of nuclear materials and weapons misuse by terrorists or even rogue states. Additionally, nuclear energy is currently the only viable alternative that can provide efficient, sustainable, and ecological coverage for the dramatically increasing current and future energy demands. Understanding the risks of IR exposure necessitates exploring how different types of IR interact with living organisms at the most fundamental level of complexity, specifically at the level of molecules and their complexes. The rising interest in radiobiology is, therefore, also driven by new experimental opportunities that enable research at previously unimaginable levels of detail and complexity. In this manuscript, we will address the important questions in radiobiology, focusing specifically on the mechanisms of radiation-induced DNA damage and repair within the context of chromatin architecture. We will emphasize the differing effects of photon and high-LET particle radiation on chromatin and DNA. Both forms of IR are encountered on Earth but are particularly significant in space.
- Keywords
- Biological effects of ionizing radiation, Chromatin architecture at micro- and nano-scale, DNA damage and repair, Densely ionizing (high-LET) particle radiation, Institute of biophysics of the Czech academy of sciences, Microscopy, Photon radiation, Radiobiological research, Single molecule localization microscopy (SMLM),
- Publication type
- Journal Article MeSH
- Review MeSH
Telomeres are nucleoprotein complexes protecting the physical ends of linear eukaryotic chromosomes and therefore helping to ensure their stability and integrity. Additionally, telomeric sequences can be localized in non-terminal regions of chromosomes, forming so-called interstitial telomeric sequences (ITSs). ITSs are traditionally considered to be relics of chromosomal rearrangements and thus very informative in the reconstruction of the evolutionary history of karyotype formation. We examined the distribution of the telomeric motifs (TTAGGG)n using fluorescence in situ hybridization (FISH) in 30 species, representing 17 families of squamate reptiles, and compared them with the collected data from another 38 species from literature. Out of the 68 squamate species analyzed, 35 possess ITSs in pericentromeric regions, centromeric regions and/or within chromosome arms. We conclude that the occurrence of ITSs is rather common in squamates, despite their generally conserved karyotypes, suggesting frequent and independent cryptic chromosomal rearrangements in this vertebrate group.
To determine the influence of increased gene expression and amplification in colorectal carcinoma on chromatin structure, the nuclear distances between pairs of bacterial artificial chromosome (BAC) clones with genomic separation from 800 to 29,000 kb were measured and compared between the tumor and parallel epithelial cells of six patients. The nuclear distances were measured between the loci in chromosomal bands 7p22.3-7p21.3; 7q35-7q36.3; 11p15.5-11p15.4; 20p13; 20p12.2; 20q11.21 and 20q12 where increased expression had been found in all types of colorectal carcinoma. The loci were visualized by three-dimensional fluorescence in situ hybridization using 22 BAC clones. Our results show that for short genomic separations, mean nuclear distance increases linearly with increased genomic separation. The results for some pairs of loci fell outside this linear slope, indicating the existence of different levels of chromatin folding. For the same genomic separations the nuclear distances were frequently shorter for tumor as compared with epithelial cells. Above the initial growing phase of the nuclear distances, a plateau phase was observed in both cell types where the increase in genomic separation was not accompanied by an increase in nuclear distance. The ratio of the mean nuclear distances between the corresponding loci in tumor and epithelium cells decreases with increasing amplification of loci. Our results further show that the large-scale chromatin folding might differ for specific regions of chromosomes and that it is basically preserved in tumor cells in spite of the amplification of many loci.
- MeSH
- Gene Amplification genetics MeSH
- Cell Nucleus genetics ultrastructure MeSH
- Chromatin genetics ultrastructure MeSH
- DNA, Neoplasm genetics MeSH
- DNA Probes MeSH
- Adult MeSH
- Epithelial Cells pathology MeSH
- In Situ Hybridization, Fluorescence MeSH
- Colorectal Neoplasms genetics pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Chromosomes, Human genetics ultrastructure MeSH
- Chromosome Banding MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Chromatin MeSH
- DNA, Neoplasm MeSH
- DNA Probes MeSH
