FS MSI refers to an accumulation of errors within microsatellite regions of DNA that lead to hypermutation and are caused by a deficient DNA mismatch repair system. The mismatch repair system serves an editing function— similar to a spellcheck mechanism—that identifies errors and removes them from the DNA. When this repair system is faulty, microsatellites in the DNA develop short nucleotide re...

The DNA mismatch repair pathway is well known for its role in correcting biosynthetic errors of DNA replication. We report here a novel role for mismatch repair in signaling programmed cell death in response to DNA damage induced by chemical carcinogens. Cells proficient in mismatch repair were highly sensitive to the cytotoxic effects of chemical carcinogens, while cells defective in either hu...

The Dam-directed post-replicative mismatch repair system of Escherichia coli removes base pair mismatches from DNA. The products of the mutH, mutL and mutS genes, among others, are required for efficient mismatch repair. Absence of any of these gene products leads to persistence of mismatches in DNA with a resultant increase in spontaneous mutation rate. To determine the specificity of the mism...

RAD3 functions in DNA repair and transcription in Saccharomyces cerevisiae and particular rad3 alleles confer a mutator phenotype, possibly as a consequence of defective mismatch correction. We assessed the potential involvement of the Rad3 protein in mismatch correction by comparing heteroduplex repair in isogenic rad3-1 and wild-type strains. The rad3-1 allele increased the spontaneous mutati...

Using random screening for genetic suppressor elements, we sought to identify portions of hMSH2 important to the ability of the mismatch repair system to recognize and process DNA adducts that mimic mismatches. All recovered candidate genetic suppressor elements were derived from the region containing amino acids 782 to 844. Expression of a peptide corresponding to this region partially disable...

DNA-binding proteins search for specific targets via facilitated diffusion along a crowded genome. However, little is known about how crowded DNA modulates facilitated diffusion and target recognition. Here we use DNA curtains and single-molecule fluorescence imaging to investigate how Msh2-Msh3, a eukaryotic mismatch repair complex, navigates on crowded DNA. Msh2-Msh3 hops over nucleosomes and...

In human cells, large DNA loop heterologies are repaired through a nick-directed pathway independent of mismatch repair. However, a 3'-nick generated by bacteriophage fd gene II protein heterology is not capable of stimulating loop repair. To evaluate the possibility that a mismatch near a loop could induce both repair types in human cell extracts, we constructed and tested a set of DNA heterod...

DNA mismatch repair is required for correcting any mismatches that are created during replication and recombination, and a defective mismatch repair system contributes to DNA damage-induced growth arrest. The colorectal cancer cell line HCT116 is known to have a mutation in the hMLH1 mismatch repair gene resulting in microsatellite instability and defective mismatch repair. Honokiol is a biphen...