Sister chromatid exchange

About: Sister chromatid exchange is a research topic. Over the lifetime, 3187 publications have been published within this topic receiving 90029 citations. The topic is also known as: replication-born DSB repair by SCE & GO:1990414.

Tumour promoter phorbol-12-myristate-13-acetate induces chromosomal damage via indirect action.

Abstract: The mouse skin tumour promoter phorbol-12-myristate-13-acetate (PMA) does not form covalent adducts with cellular DNA and its mutagenic potency in several systems is low or absent1–6. There have been conflicting reports of the capacity of PMA to produce sister chromatid exchanges (SCEs)3,6–8. As PMA induces the formation of superoxide radicals in polymorphonuclear leukocytes and mitogen-stimulated lymphocytes9–11, we suggested that it might produce DNA damage via indirect action by the formation of intermediate active oxygen species12,13. As is typical for other DNA-damaging agents which mainly act indirectly, for example, ionizing radiation, PMA would be expected to have low mutagenicity but high clastogenic (chromosome-breaking) activity14. In agreement with this, we report here that PMA, but not its weakly or non-promoting derivatives, induced chromosomal aberrations with high efficiency in phytohaemagglutinin (PHA)-stimulated human lymphocytes, but was only a weak producer of SCE. This activity was suppressed by superoxide dismutase, which catalyses the breakdown of superoxide radicals.

Sister chromatid fusion initiates amplification of the dihydrofolate reductase gene in Chinese hamster cells.

Abstract: We have utilized a dihydrofolate reductase (DHFR) probe in combination with selected probes from other positions along the 2q chromosome arm in a two-color fluorescence in situ hybridization analysis of early DHFR gene amplification events in CHO cells. These studies show clearly that the most frequent initiating event is the formation of a giant inverted duplication, resulting either from chromosome breakage and terminal fusion or a reverse unequal sister chromatid exchange. The dicentric chromosomes thus formed initiate bridge/breakage/fusion cycles that appear to mediate subsequent amplification steps to higher copy number.

Targeted inactivation of p53 in human cells does not result in aneuploidy.

Abstract: Because p53 mutation and aneuploidy usually coexist, it has been suggested that p53 inactivation leads to aneuploidy. We have rigorously tested this hypothesis in diploid human cell lines in which p53 was experimentally inactivated by targeted homologous recombination. Cells completely deficient in p53 did not become aneuploid, although a slight tendency toward tetraploidization was observed. No increased rates of numerical or structural chromosomal instabilities were observed in the p53-deficient cells. Rates of sister chromatid exchange and homologous recombination were also unaffected by p53 status. These results show that inactivation of p53 does not, in and of itself, lead to the development of aneuploidy.

Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway

Abstract: Werner Syndrome (WS) is characterized by premature aging, genomic instability, and cancer. The combined impact of WRN helicase deficiency and limiting telomere reserves is central to disease pathogenesis. Here, we report that cells doubly deficient for telomerase and WRN helicase show chromosomal aberrations and elevated recombination rates between telomeres of sister chromatids. Somatic reconstitution of WRN function, but not a WRN helicase-deficient mutant, abolished telomere sister chromatid exchange (T-SCE), indicating that WRN normally represses T-SCEs. Elevated T-SCE was associated with greater immortalization potential and resultant tumors maintained telomeres via the alternative lengthening of telomere (ALT) pathway. We propose that the increased incidence of chromosomal instability and cancer in WS relates in part to aberrant recombinations between sister chromatids at telomeres, which facilitates the activation of ALT and engenders cancer-relevant chromosomal aberrations and tumor formation.

Increased frequency of sister chromatid exchanges in cigarette smokers.

Abstract: The analysis of sister chromatid exchange (SCE) might be a useful technique for the study of genetic damage in humans exposed to environmental mutagens and carcinogens. To obtain reference values for such studies we have analysed SCE-frequencies in peripheral lymphocytes of 43 healthy, occupationally non-exposed human subjects. Among these subjects cigarette smokers were found to have significantly higher SCE-frequencies (16.2±SD 3.6) than non-smokers (13.1±2.9). When smokers were subdivided into moderate (<10 cig. per day) and heavy (≥10cig. per day) smokers, a clear dose-effect of smoking on the SCE frequency was noted. This observation was supported by a retrospective inquiry into the smoking habits of 18 previously analysed psoriasis patients, among whom SCE-frequencies of 16.8±2.4 and 13.7±3.1 were recorded for smokers and non-smokers, respectively. In a group of 19 laboratory workers there was no significant difference between smokers (18.6±3.3) and non-smokers (19.5±5.0). The significantly increased SCE-frequencies recorded in this group support earlier observations and strongly suggest occupational exposure as a causative factor. The present results indicate that the SCE-frequency in healthy human subjects is influenced by individual smoking habits as well.