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Molecular and Cellular Biology, May 2001, p. 3425-3435, Vol. 21, No. 10
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.
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
*
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.
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