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DNA Mismatch Repair Introduces Mutations in Non-Dividing Cells

Yoke Wah Kow, Ph.D., Gray F. Crouse, Ph.D.
Emory University
NIEHS Grant P01ES011163

 

NIEHS grantees report a role for DNA mismatch repair in creating mutations in non-dividing cells. These mutations can lead to cancer or create beneficial new phenotypes.

DNA mismatch repair removes replication errors by removing mismatched nucleotides. It is a strand-specific process, meaning the process removes only nucleotides on the newly replicated strand of DNA. How eukaryotic cells distinguish the strands is not fully understood, but the cells likely lose the ability to distinguish the strands as replication proceeds.

The researchers introduced specific mispairs into the DNA of yeast cells in a way that let them observe the very rare event of non-strand dependent DNA repair. They found that mispairs, not repaired during replication, sometimes underwent mismatch repair later when the cells were no longer dividing. This repair was not strand dependent and sometimes introduced mutations into the DNA sequence that allowed cells to resume growth. In one case, they observed such mutations arising in cells that had been in a non-dividing state for several days.

 


Citation: Rodriguez GP, Romanova NV, Bao G, Rouf NC, Kow YW, Crouse GF. 2012. Mismatch repair-dependent mutagenesis in nondividing cells. Proc Natl Acad Sci U S A 109(16):6153-6158.


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