Effect of DNA Sequence Divergence on Homologous Recombination as Analyzed by a Random-Walk Model

Author:

Fujitani Youhei1,Kobayashi Ichizo2

Affiliation:

1. Department of Applied Physics and Physico-Informatics, Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan

2. Department of Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

Abstract

Abstract A point connecting a pair of homologous regions of DNA duplexes moves along the homology in a reaction intermediate of the homologous recombination. Formulating this movement as a random walk, we were previously successful at explaining the dependence of the recombination frequency on the homology length. Recently, the dependence of the recombination frequency on the DNA sequence divergence in the homologous region was investigated experimentally; if the methyl-directed mismatch repair (MMR) system is active, the logarithm of the recombination frequency decreases very rapidly with an increase of the divergence in a low-divergence regime. Beyond this regime, the logarithm decreases slowly and linearly with the divergence. This “very rapid drop-off” is not observed when the MMR system is defective. In this article, we show that our random-walk model can explain these data in a straightforward way. When a connecting point encounters a diverged base pair, it is assumed to be destroyed with a probability that depends on the level of MMR activity.

Publisher

Oxford University Press (OUP)

Subject

Genetics

Reference29 articles.

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2. Dual roles for DNA sequence identity and the mismatch repair system in the regulation of mitotic crossing-over in yeast;Datta;Proc. Natl. Acad. Sci. USA,1997

3. Reexamination of the gene targeting frequency as a function of the extent of homology between the targeting vector and the target locus;Deng;Mol. Cell. Biol.,1992

4. Diffusion in systems with static disorder;Denteneer;Phys. Rev. B,1984

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