John C Game, Lawrence Berkeley National Laboratory, Berkeley, California, USA
Published online: December 2001
DOI: 10.1038/npg.els.0000578
DNA double-strand breaks and other damage can be repaired in cells by a process involving recombination with an undamaged homologous molecule. This is related to the recombination that occurs naturally during meiosis in most eukaryotes, and many of the same gene products are needed for both processes.
Keywords: recombination; repair; double-strand breaks; Saccharomyces cerevisiae; RAD genes
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Figure 1. Model for the early steps of recombination in S. cerevisiae. Each line represents a single DNA strand and arrows indicate the 3¢ direction. (a) A double-strand break (DSB) on one chromatid initiates recombination. (b) 5¢ to 3¢ digestion occurs on each side of the DSB to leave 3¢ single-stranded regions. (c) One of these single-stranded tails invades the unbroken duplex, displacing one of its strands and generating heteroduplex DNA. (d) Synthesis primed by the invading 3¢ end displaces more of the unbroken strand, which anneals with the other single-stranded region on the broken duplex, to generate a second heteroduplex region. (e) Resynthesis fills the remaining single-stranded region, using the unbroken strand as a template. Ligation of both resynthesized regions with existing strands generates a double Holliday junction. If the heteroduplex DNA includes a heterozygosity, correction of the mismatched site (shown here as A/a) will either restore a/a or generate A/A information. Since the two uninvolved chromatids (not shown) contribute one A and one a gamete, this leads to 2A:2a or 3A:1a segregations respectively. The structure shown in (e) can be resolved by topoisomerase action or by cutting two strands at each junction. The disposition of outside markers is determined by which strands are cut. Reproduced from Sun et al. (
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| References | |
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| Further Reading | |
| Benjamin MB, Potter H, Yandell DW and Little JB (1991) A system for assaying homologous recombination at the endogenous human thymidine kinase gene. Proceedings of the National Academy of Sciences of the USA 88: 6652–6656. | |
| book Friedberg EC, Walker GC and Siede W (1995) DNA Repair and Mutagenesis. Washington, DC: ASM Press. | |
| Game JC (1993) DNA double-strand breaks and the RAD50-RAD57 genes in Saccharomyces. Seminars in Cancer Biology 4: 73–83. | |
| Haber JE (1995) In vivo biochemistry: physical monitoring of recombination induced by site-specific endonucleases. BioEssays 17: 609–620. | |
| Holliday R (1964) A mechanism for gene conversion in fungi. Genetical Research 5: 282–304. | |
| Jeggo PA (1998) DNA breakage and repair. Advances in Genetics 38: 185–218. | |
| Meselson MS and Radding CM (1975) A general model for genetic recombination. Proceedings of the National Academy of Sciences of the USA 72: 358–361. | |
| Osman F and Subramani S (1998) Double-strand break-induced recombination in eukaryotes. Progress in Nucleic Acid Research and Molecular Biology 58: 263–299. | |
| book Petes TD, Malone RE and Symington LS (1991) "Recombination in yeast". In: Broach JR, Jones EW and Pringle JR (eds) The Molecular and Cellular Biology of the Yeast S. cerevisiae: Genome Dynamics, Protein Synthesis, and Energetics, pp. 407–521. New York: Cold Spring Harbor Laboratory Press. | |
| Stahl F (1996) Meiotic recombination in yeast: Coronation of the double-strand-break repair model. Cell 87: 965–968. | |
| Usui T, Ohta T, Oshiumi H, Tomizawa J, Ogawa H and Ogawa T (1998) Complex formation and functional versatility of Mre11 of budding yeast in recombination. Cell 95: 705–716. | |
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