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Science. 2011 Dec 23;334(6063):1713-6. doi: 10.1126/science.1210770.

Mismatch repair, but not heteroduplex rejection, is temporally coupled to DNA replication.

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Ludwig Institute for Cancer Research, Departments of Medicine and Cellular and Molecular Medicine and Cancer Center, Moores-UCSD Cancer Center, University of California School of Medicine-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0669, USA.


In eukaryotes, it is unknown whether mismatch repair (MMR) is temporally coupled to DNA replication and how strand-specific MMR is directed. We fused Saccharomyces cerevisiae MSH6 with cyclins to restrict the availability of the Msh2-Msh6 mismatch recognition complex to either S phase or G2/M phase of the cell cycle. The Msh6-S cyclin fusion was proficient for suppressing mutations at three loci that replicate at mid-S phase, whereas the Msh6-G2/M cyclin fusion was defective. However, the Msh6-G2/M cyclin fusion was functional for MMR at a very late-replicating region of the genome. In contrast, the heteroduplex rejection function of MMR during recombination was partially functional during both S phase and G2/M phase. These results indicate a temporal coupling of MMR, but not heteroduplex rejection, to DNA replication.

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