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Recombinational repair of diverged DNAs : a study of homoeologous chromosomes and mammalian YACs in yeast

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Summary

Recombinational repair is the means by which DNA double-strand breaks (DSBs) are repaired in yeast. DNA divergence between chromosomes was shown previously to inhibit repair in diploid G1 cells, resulting in chromosome loss at low nonlethal doses of ionizing radiation. Furthermore, 15–20% divergence prevents meiotic recombination between individual pairs of Saccharomyces cerevisiae and S. carlsbergensis chromosomes in an otherwise S. cerevisiae background. Based on analysis of the efficiency of DSB-induced chromosome loss and direct genetic detection of intragenic recombination, we conclude that limited DSB recombinational repair can occur between homoeologous chromosomes. There is no difference in loss between a repair-proficient Pms+ strain and a mismatch repair mutant, pms1. Since DSB recombinational repair is tolerant of diverged DNAs, this type of repair could lead to novel genes and altered chromosomes. The sensitivity to DSB-induced loss of 11 individual yeast artificial chromosomes (YACs) containing mouse or human (chromosome 21 or HeLa) DNA was determined. Recombinational repair between a pair of homologous HeLa YACs appears as efficient as that between homologous yeast chromosomes in that there is no loss at low radiation doses. Single YACs exhibited considerable variation in response, although the response for individual YACs was highly reproducible. Based on the results with the yeast homoeologous chromosomes, we propose that the potential exists for intra- YAC recombinational repair between diverged repeat DNA and that the extent of repair is dependent upon the amount of repeat DNA and the degree of divergence. The sensitivity of YACs containing mammalian DNA to ionizing radiation-induced loss may thus be an indicator of the extent of repeat DNA.

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Authors and Affiliations

  1. Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences (NIH), 27709, Research Triangle Park, NC, USA

    Michael A. Resnick & James Westmoreland

  2. Laboratory of Biology and Microbial Genetics, University of Zagreb, Krsnjavoga 25, 4100, Zagreb, Croatia

    Zoran Zgaga

  3. Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA

    Philip Hieter

  4. Department of Plant Biology, University of California, 94720, Berkeley, CA, USA

    Seymour Fogel

  5. Institute of Genetics, University of Copenhagen, O. Farimagsgade 2A, DK-1353, Copenhagen K, Denmark

    Torsten Nilsson-Tillgren

Authors
  1. Michael A. Resnick
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  2. Zoran Zgaga
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  3. Philip Hieter
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  4. James Westmoreland
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  5. Seymour Fogel
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  6. Torsten Nilsson-Tillgren
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Communicated by B.J. Kilbey

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Resnick, M.A., Zgaga, Z., Hieter, P. et al. Recombinational repair of diverged DNAs : a study of homoeologous chromosomes and mammalian YACs in yeast. Molec. Gen. Genet. 234, 65–73 (1992). https://doi.org/10.1007/BF00272346

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