Topic
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.
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TL;DR: Analysis of sister chromatid exchanges may permit more sensitive detection of damage to DNA caused by other agents than has previously been possible by classical cytological techniques.
Abstract: Sister chromatid exchanges in chromosomes from human lymphocytes grown two replication cycles in medium containing 5-bromodeoxyuridine can be detected by fluorescence microscopy after staining with the bisbenzimidazole dye 33258 Hoechst. These exchanges are much more frequent than chromosome or chromatid breaks and appear to be partly but not entirely due to 5-bromodeoxyuridine incorporation. Sister chromatid exchanges are extremely sensitive indicators of chromosome damage produced by DNA cross-linking agents such as mitomycin C. Significant increases in the sister chromatid exchange frequency occur with 3 ng/ml of mitomycin C; higher concentrations of mitomycin C induce further sister chromatid exchanges. Comparatively few gross chromosomal aberrations are seen in cells exhibiting as many as one hundred or more sister chromatid exchanges. Most of the damage caused by mitomycin C to chromosomal DNA is apparently repaired without detectable changes in chromosome morphology. Analysis of sister chromatid exchanges may permit more sensitive detection of damage to DNA caused by other agents than has previously been possible by classical cytological techniques.
474 citations
TL;DR: Findings show that HR uses the nascent sister chromatid to repair potentially lethal DNA lesions accompanying replication, which might explain the lethality or tumorigenic potential associated with defects in HR or HR-associated proteins.
Abstract: Sister chromatid exchange (SCE) frequency is a commonly used index of chromosomal stability in response to environmental or genetic mutagens. However, the mechanism generating cytologically detectable SCEs and, therefore, their prognostic value for chromosomal stability in mitotic cells remain unclear. We examined the role of the highly conserved homologous recombination (HR) pathway in SCE by measuring SCE levels in HR-defective vertebrate cells. Spontaneous and mitomycin C-induced SCE levels were significantly reduced for chicken DT40 B cells lacking the key HR genes RAD51 and RAD54 but not for nonhomologous DNA end-joining (NHEJ)-defective KU70(-/-) cells. As measured by targeted integration efficiency, reconstitution of HR activity by expression of a human RAD51 transgene restored SCE levels to normal, confirming that HR is the mechanism responsible for SCE. Our findings show that HR uses the nascent sister chromatid to repair potentially lethal DNA lesions accompanying replication, which might explain the lethality or tumorigenic potential associated with defects in HR or HR-associated proteins.
436 citations
TL;DR: It is revealed that yeast Eco1 and its human ortholog, ESCO1, both acetylate Smc3, a component of the cohesin complex that physically holds the sister chromatid together, at two conserved lysine residues.
403 citations
TL;DR: The cloning and function of the human XRCC1 gene is described, which is the first mammalian gene isolated that affects cellular sensitivity to ionizing radiation and appears to be missing approximately 100 bp of transcribed sequence, including 26 nucleotides of coding sequence.
Abstract: We describe the cloning and function of the human XRCC1 gene, which is the first mammalian gene isolated that affects cellular sensitivity to ionizing radiation. The CHO mutant EM9 has 10-fold-higher sensitivity to ethyl methanesulfonate, 1.8-fold-higher sensitivity to ionizing radiation, a reduced capacity to rejoin single-strand DNA breaks, and a 10-fold-elevated level of sister chromatid exchange compared with the CHO parental cells. The complementing human gene was cloned from a cosmid library of a tertiary transformant. Two cosmid clones produced transformants that showed approximately 100% correction of the repair defect in EM9 cells, as determined by the kinetics of strand break repair, cell survival, and the level of sister chromatid exchange. A nearly full-length clone obtained from the pcD2 human cDNA expression library gave approximately 80% correction of EM9, as determined by the level of sister chromatid exchange. Based on an analysis of the nucleotide sequence of the cDNA insert compared with that of the 5' end of the gene from a cosmid clone, the cDNA clone appeared to be missing approximately 100 bp of transcribed sequence, including 26 nucleotides of coding sequence. The cDNA probe detected a single transcript of approximately 2.2 kb in HeLa polyadenylated RNA by Northern (RNA) blot hybridization. From the open reading frame and the positions of likely start sites for transcription and translation, the size of the putative XRCC1 protein is 633 amino acids (69.5 kDa). The size of the XRCC1 gene is 33 kb, as determined by localizing the endpoints on a restriction endonuclease site map of one cosmid clone. The deduced amino acid sequence did not show significant homology with any protein in the protein sequence data bases examined.
402 citations
TL;DR: The frequency of unequal crossing over, as measured by the deletion or duplication of an inserted genetic marker (LEU2), is sufficient to maintain the sequence homogeneity of the rDNA repeat units.
Abstract: Unequal sister chromatid exchanges occur at the ribosomal DNA locus of yeast during mitotic growth. The frequency of unequal crossing over, as measured by the deletion or duplication of an inserted genetic marker (LEU2), is sufficient to maintain the sequence homogeneity of the rDNA repeat units.
395 citations