Elevated rates of sister chromatid exchange at chromosome ends
| Autor: | Cynthia Friedman, Li Hsu, M. Katharine Rudd, Elena V. Linardopoulou, Sean S Parghi, Barbara J. Trask |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Primates
Cancer Research lcsh:QH426-470 DNA repair Molecular Sequence Data Sister chromatid exchange Biology Models Biological 03 medical and health sciences 0302 clinical medicine Homo (Human) Tumor Cells Cultured Genetics Chromosomes Human Humans Molecular Biology Mitosis In Situ Hybridization Fluorescence Genetics (clinical) Ecology Evolution Behavior and Systematics 030304 developmental biology 0303 health sciences Chromosome Genetics and Genomics Telomere Subtelomere Molecular biology lcsh:Genetics Oncology 030220 oncology & carcinogenesis Chromatid Homologous recombination Sister Chromatid Exchange Research Article |
| Zdroj: | PLoS Genetics, Vol 3, Iss 2, p e32 (2007) PLoS Genetics |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Chromosome ends are known hotspots of meiotic recombination and double-strand breaks. We monitored mitotic sister chromatid exchange (SCE) in telomeres and subtelomeres and found that 17% of all SCE occurs in the terminal 0.1% of the chromosome. Telomeres and subtelomeres are significantly enriched for SCEs, exhibiting rates of SCE per basepair that are at least 1,600 and 160 times greater, respectively, than elsewhere in the genome. Author Summary The ends of chromosomes are evolutionarily dynamic and structurally unusual parts of the human genome. Arrays of telomeric repeats cap each end and protect chromosomes from degradation and end-to-end fusions. Just inside the telomeres are patchworks of larger DNA segments duplicated on different chromosome ends. These subtelomeric duplications reflect the high frequency with which DNA breaks in these regions were healed by interchromosomal repair processes during recent primate evolution. In this study, we asked if chromosomal ends are also unusually susceptible to replication-induced DNA breaks and repair during mitotic division of somatic cells. We employed a specialized fluorescent technique to measure sister chromatid exchange (SCE) specifically in telomeres and subtelomeres, as such events would be missed by standard SCE-detection methods. We find extraordinarily high rates of SCE in these terminal regions: over 15% of observed SCEs occur in just 0.1% of the genome. Thus, chromosome ends are hotspots of DNA breaks and recombinational repair in mitosis, as shown previously in meiosis. The enrichment of DNA breaks at chromosome ends contributes to normal variation, chromosome evolution, and chromosome rearrangements leading to disease. |
| Databáze: | OpenAIRE |
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