Eukaryotic Recombination: Initiation by Double‐strand Breaks

A double-strand break in one deoxyribonucleic acid (DNA) double helix, possibly caused by DNA damaging agents such as ionizing radiation or normal metabolic processes, stimulates repair by a pathway of recombination that uses a second unbroken DNA double helix containing homologous sequences as a donor of genetic information to restore the intact DNA structure.

Keywords: DNA repair; double-strand break; genome stability; recombination

Figure 1. Two models for double-strand break (DSB)-induced recombination. Following a double-strand break in one DNA helix, a processed end can invade a homologous template to initiate repair. This process may either proceed by a replication-based mechanism that results in gene conversion products, or by the classical double-strand repair model that can result in both crossover and noncrossover products, depending on resolution of the Holliday junction intermediate.
Figure 2. Model for mating-type switching in yeast. Following a double-strand break at one locus by the HO endonuclease, invasion of a single-strand tail from the broken MAT locus into the unbroken donor leads to a replication-based recombination event in which gene conversion leads to mating-type switching.
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 References
    Chen J, Silver DP, Walpita D et al. (1998) Stable interaction between proteins of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. Molecular Cell 2: 317–328.
    Cohen-Tannoudji M, Robine S, Choulika A et al. (1998) I-SceI-induced gene replacement at a natural locus in embryonic stem cells. Molecular and Cellular Biology 18: 1444–1448.
    Colleaux L, d'Auriol L, Betermier M et al. (1986) Universal code equivalent of a yeast mitochondrial intron reading frame is expressed into E. coli as a specific double strand endonuclease. Cell 44: 521–533.
    Keeney S and Kleckner N (1997) Meiosis-specific double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell 88: 375–384.
    Liang F, Han M, Romanienko PJ and Jasin M (1998) Homology-directed repair is a major double-strand break repair pathway in mammalian cells. Proceedings of the National Academy of Sciences of the USA 95: 5172–5177.
    Moynahan ME and Jasin M (1997) Loss of heterozygosity induced by a chromosomal double-strand break. Proceedings of the National Academy of Sciences of the USA 94: 8988–8993.
    Paques F, Leung W and Haber J (1998) Expansions and contractions in a tandem repeat induced by double-strand break repair. Molecular and Cellular Biology 18: 2045–2054.
    Richardson C, Moynahan ME and Jasin M (1998) Double-strand break repair by interchromosomal recombination: suppression of chromosomal translocations. Genes and Development 12: 3831–3842.
    Szostak JW, Orr-Weaver TL, Rothstein RJ and Stahl FW (1983) The double-strand-break repair model for recombination. Cell 33: 25–35.
    Waldman AS and Liskay RM (1987) Differential effects of base-pair mismatch on intrachromosomal versus extrachromosomal recombination in mouse cells. Proceedings of the National Academy of Sciences of the USA 84: 5340–5344.
 Further Reading
    Haber JE (1998) Mating-type switching in yeast. Annual Review of Genetics 32: 561–599.
    Jasin M (1996) Genetic manipulation of genomes with rare-cutting endonucleases. Trends in Genetics 12: 224–228.
    book Jasin M (2000) "Double-strand break repair and homologous recombination in mammalian cells". In: Nickoloff JA and Hoekstra MF (eds) DNA Damage and Repair. Vol. 3: DNA Repair in Mammalian Systems. Totowa, NJ: Humana Press.
    Lewis SM (1994) The mechanism of V(D)J joining: lessons from molecular, immunological and comparative analyses. Advances in Immunology 56: 27–149.
    book Nickoloff JA and Hoekstra MF (1998) "Double-strand break and recombinational repair in Saccharomyces cerevisiae". In: Nickoloff JA and Hoekstra MF (eds) DNA Damage and Repair. Vol. 1: DNA Repair in Prokaryotes and Lower Eukaryotes. Totowa, NJ: Humana Press.
    book Richardson C, Elliott B and Jasin M (1999) "Chromosomal double-strand breaks introduced in mammalian cells by expression of I-SceI endonuclease". In: Henderson D (ed.) DNA Repair Protocols: Eukaryotic Systems, pp. 453–464. Totowa, NJ: Humana Press.
    Schwacha A and Kleckner N (1995) Identification of double Holliday junctions as intermediates in meiotic recombination. Cell 76: 51–63.
    Shinohara A and Ogawa T (1995) Homologous recombination and the roles of double-strand breaks. Trends in Biochemical Sciences 237: 387–390.
    Stahl F (1996) Meiotic recombination in yeast: coronation of the double-strand-break repair model. Cell 87: 965–968.
    book Subramani S and Seaton BL (1988) "Homologous recombination in mitotically dividing mammalian cells". In: Kucherlapati R and Smith GR (eds) Genetic Recombination, pp. 549–573. Washington, DC: American Society for Microbiology
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Richardson, Christine, and Jasin, Maria(Apr 2001) Eukaryotic Recombination: Initiation by Double‐strand Breaks. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000577]