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Molecular and Cellular Biology, May 2001, p. 3425-3435, Vol. 21, No. 10
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.10.3425-3435.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Evidence for Biased Holliday Junction Cleavage and Mismatch Repair Directed by Junction Cuts during Double-Strand-Break Repair in Mammalian Cells

Mark D. Baker1,2,* and Erin C. Birmingham2

Department of Molecular Biology and Genetics1 and Department of Pathobiology,2 University of Guelph, Guelph, Ontario, Canada N1G 2W1

Received 11 January 2001/Returned for modification 15 February 2001/Accepted 23 February 2001

In mammalian cells, several features of the way homologous recombination occurs between transferred and chromosomal DNA are consistent with the double-strand-break repair (DSBR) model of recombination. In this study, we examined the segregation patterns of small palindrome markers, which frequently escape mismatch repair when encompassed within heteroduplex DNA formed in vivo during mammalian homologous recombination, to test predictions of the DSBR model, in particular as they relate to the mechanism of crossover resolution. According to the canonical DSBR model, crossover between the vector and chromosome results from cleavage of the joint molecule in two alternate sense modes. The two crossover modes lead to different predicted marker configurations in the recombinants, and assuming no bias in the mode of Holliday junction cleavage, the two types of recombinants are expected in equal frequency. However, we propose a revision to the canonical model, as our results suggest that the mode of crossover resolution is biased in favor of cutting the DNA strands upon which DNA synthesis is occurring during formation of the joint molecule. The bias in junction resolution permitted us to examine the potential consequences of mismatch repair acting on the DNA breaks generated by junction cutting. The combination of biased junction resolution with both early and late rounds of mismatch repair can explain the marker patterns in the recombinants.

* Corresponding author. Mailing address: Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1. Phone: (519) 824-4120 ext. 4788. Fax: (519) 824-5930. E-mail: mdbaker{at}uoguelph.ca.

Molecular and Cellular Biology, May 2001, p. 3425-3435, Vol. 21, No. 10
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.10.3425-3435.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • McCulloch, R. D., Baker, M. D. (2006). Analysis of one-sided marker segregation patterns resulting from Mammalian gene targeting.. Genetics 172: 1767-1781 [Abstract] [Full Text]  
  • Birmingham, E. C., Lee, S. A., McCulloch, R. D., Baker, M. D. (2004). Testing Predictions of the Double-Strand Break Repair Model Relating to Crossing Over in Mammalian Cells. Genetics 168: 1539-1555 [Abstract] [Full Text]  
  • Stahl, F. W., Foss, H. M., Young, L. S., Borts, R. H., Abdullah, M. F. F., Copenhaver, G. P. (2004). Does Crossover Interference Count in Saccharomyces cerevisiae?. Genetics 168: 35-48 [Abstract] [Full Text]  
  • Read, L. R., Raynard, S. J., Ruksc, A., Baker, M. D. (2004). Gene repeat expansion and contraction by spontaneous intrachromosomal homologous recombination in mammalian cells. Nucleic Acids Res 32: 1184-1196 [Abstract] [Full Text]  
  • McCulloch, R. D., Read, L. R., Baker, M. D. (2003). Strand Invasion and DNA Synthesis From the Two 3' Ends of a Double-Strand Break in Mammalian Cells. Genetics 163: 1439-1447 [Abstract] [Full Text]  
  • Raynard, S. J., Baker, M. D. (2002). Incorporation of Large Heterologies Into Heteroduplex DNA During Double-Strand-Break Repair in Mouse Cells. Genetics 162: 977-985 [Abstract] [Full Text]  


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