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Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6153-8. doi: 10.1073/pnas.1115361109. Epub 2012 Apr 2.

Mismatch repair-dependent mutagenesis in nondividing cells.

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  • 1Department of Biology, Department of Radiation Oncology, and Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.


Mismatch repair (MMR) is a major DNA repair pathway in cells from all branches of life that removes replication errors in a strand-specific manner, such that mismatched nucleotides are preferentially removed from the newly replicated strand of DNA. Here we demonstrate a role for MMR in helping create new phenotypes in nondividing cells. We show that mispairs in yeast that escape MMR during replication can later be subject to MMR activity in a replication strand-independent manner in nondividing cells, resulting in either fully wild-type or mutant DNA sequence. In one case, this activity is responsible for what appears to be adaptive mutation. This replication strand-independent MMR activity could contribute to the formation of tumors arising in nondividing cells and could also contribute to mutagenesis observed during somatic hypermutation of Ig genes.

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