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.

Chromosomal aberrations and sister chromatid exchange tests in Chinese hamster ovary cells in vitro. IV. Results with 15 chemicals.

Abstract: Forty-six coded chemicals were tested for their ability to induce sister chromatid exchanges (SCEs) and chromosomal aberrations (ABs) in cultured Chinese hamster ovary (CHO) cells using a standard protocol with and without exogenous metabolic activation. Sixteen chemicals were negative and 15 were positive in both assays; 15 were positive for SCEs only (one chemical that was positive for SCEs was equivocal for ABs), and no chemicals induced ABs only. The effect of cell harvest time on the ability to detect the induction of ABs was examined for 18 chemicals. Seven chemicals produced a positive response using both standard and extended harvest times, five were positive only using an extended harvest time, and six were negative using both harvest times. The relationship between cell cycle delay and SCE induction was also examined, and the two appear to be unrelated.

Extracellular factor(s) following exposure to α particles can cause sister chromatid exchanges in normal human cells

Abstract: The mechanism(s) by which α particles like those emitted from inhaled radon and radon progeny cause their mutagenic and carcinogenic effects remains unclear. Although direct nuclear traversals by α particles may be involved in mediating these outcomes, increasing evidence indicates that α particles can cause alterations in DNA in the absence of direct “hits” to cell nuclei. Using the occurrence of excessive sister chromatid exchanges (SCEs) as an index of DNA damage in human lung fibroblasts, we investigated the hypothesis that α particles may induce DNA damage via the generation of extracellular factors. We have found that a relatively low dose of α particles indeed results in the generation of extracellular factors, which, upon transfer to unexposed normal human cells, can cause excessive SCEs to an extent equivalent to that observed when the cells are directly irradiated with the same irradiation dose. A short-lived, SCE-inducing factor(s) was generated in α-irradiated culture medium containing serum in the absence of cells; it was found that the activity of this factor can be promptly inhibited by superoxide dismutase. A more persistent SCE-inducing factor(s), which can survive freeze-thawing, is heat labile and also can be inhibited by superoxide dismutase, was produced by fibroblasts after exposure to α particles. These results indicate that the initiating target for α-particle-induced genetic changes can be larger than the nuclear compartment alone and even larger than the cytoplasmic compartment. How transmissible factors like those observed here in vitro may extend to the in vivo condition in the context of α-particle-induced carcinogenesis in the respiratory tract and elsewhere remains to be determined.

Human Bub1 protects centromeric sister-chromatid cohesion through Shugoshin during mitosis

Abstract: Sister chromatids in mammalian cells remain attached mostly at their centromeres at metaphase because of the loss of cohesion along chromosome arms in prophase. Here, we report that Bub1 retains centromeric cohesion in mitosis of human cells. Depletion of Bub1 or Shugoshin (Sgo1) in HeLa cells by RNA interference causes massive missegregation of sister chromatids that originates at centromeres. Surprisingly, loss of chromatid cohesion in Bub1 and Sgo1 RNA-interference cells does not appear to require the full activation of separase but, instead, triggers a mitotic arrest that depends on Mad2 and Aurora B. Bub1 maintains the steady-state levels and centromeric localization of Sgo1. Therefore, Bub1 protects centromeric cohesion through Shugoshin in mitosis.

Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double‐strand breaks

Abstract: The structural maintenance of chromosomes (SMC) family of proteins has been implicated in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). The SMC1/3 cohesin complex is thought to promote HR by maintaining the close proximity of sister chromatids at DSBs. The SMC5/6 complex is also required for DNA repair, but the mechanism by which it accomplishes this is unclear. Here, we show that RNAi-mediated knockdown of the SMC5/6 complex components in human cells increases the efficiency of gene targeting due to a specific requirement for hSMC5/6 in sister chromatid HR. Knockdown of the hSMC5/6 complex decreases sister chromatid HR, but does not reduce nonhomologous end-joining (NHEJ) or intra-chromatid, homologue, or extrachromosomal HR. The hSMC5/6 complex is itself recruited to nuclease-induced DSBs and is required for the recruitment of cohesin to DSBs. Our results establish a mechanism by which the hSMC5/6 complex promotes DNA repair and suggest a novel strategy to improve the efficiency of gene targeting in mammalian somatic cells.

Molecular mechanisms of sister-chromatid exchange.

Abstract: Sister-chromatid exchange (SCE) is the process whereby, during DNA replication, two sister chromatids break and rejoin with one another, physically exchanging regions of the parental strands in the duplicated chromosomes. This process is considered to be conservative and error-free, since no information is generally altered during reciprocal interchange by homologous recombination. Upon the advent of non-radiolabel detection methods for SCE, such events were used as genetic indicators for potential genotoxins/mutagens in laboratory toxicology tests, since, as we now know, most forms of DNA damage induce chromatid exchange upon replication fork collapse. Much of our present understanding of the mechanisms of SCE stems from studies involving nonhuman vertebrate cell lines that are defective in processes of DNA repair and/or recombination. In this article, we present a historical perspective of studies spearheaded by Dr. Anthony V. Carrano and colleagues focusing on SCE as a genetic outcome, and the role of the single-strand break DNA repair protein XRCC1 in suppressing SCE. A more general overview of the cellular processes and key protein "effectors" that regulate the manifestation of SCE is also presented.