UV damage endonuclease (Uve1p) from Schizosaccharomyces pombe was initially described as a DNA repair enzyme specific for the repair of UV light-induced photoproducts and proposed as the initial step in an alternative excision repair pathway. Here we present biochemical and genetic evidence demonstrating that Uve1p is also a mismatch repair endonuclease which recognizes and cleaves DNA 5' to th...

Tumors defective for DNA polymerase (Pol) e proofreading have the highest tumor mutation burden identified. A major unanswered question is whether loss of Pol e proofreading by itself is sufficient to drive this mutagenesis, or whether additional factors are necessary. To address this, we used a combination of next generation sequencing and in vitro biochemistry on human cell lines engineered t...

DNA mismatch binding in vitro, resistance to DNA methylation damage, and spontaneous mutation rates were examined in human colorectal adenocarcinoma cell lines. Of 11 cell lines, 3 (DLD1, HCT15, and LoVo) were defective in mismatch binding. All three lines had a mutator phenotype. These properties indicate that DLD1 and HCT15 may, like LoVo, carry mutations in the mismatch recognition protein h...

Mismatch repair reverses replication errors and inhibits recombination between diverged sequences. This has been suggested to be important in speciation, especially in prokaryotes, but theoretical analysis indicates that genetic divergence in bacterial populations is not constrained by naturally occurring recombination levels.

Distraction of goal-oriented performance by a sudden change in the auditory environment is an everyday life experience. Different types of changes can be distracting, including a sudden onset of a transient sound and a slight deviation of otherwise regular auditory background stimulation. With regard to deviance detection, it is assumed that slight changes in a continuous sequence of auditory s...

Gene conversion, non-reciprocal transfer from one homologous sequence to another, is a major force in evolutionary dynamics, promoting co-evolution in gene families and maintaining similarities between repeated genes. However, the properties of the transfer - where it initiates, how far it proceeds and how the resulting conversion tracts are affected by mismatch repair - are not well understood...

In this issue of Structure, Cho and colleagues provide intriguing insight into the first steps of the DNA mismatch repair process. By using single-molecule techniques, they show that the protein MutS undergoes two different types of diffusion on error-containing DNA in an ATP-dependent way.

DNA double-strand break (DSB) repair in yeast is effected primarily by gene conversion. Conversion can conceivably result from gap repair or from mismatch repair of heteroduplex DNA (hDNA) in recombination intermediates. Mismatch repair is normally very efficient, but unrepaired mismatches segregate in the next cell division, producing sectored colonies. Conversion of small heterologies (single...

DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects mismatches generated during DNA replication and escape proofreading. MMR proteins also participate in many other DNA transactions, such that inactivation of MMR can have wide-ranging biological consequences, which can be either beneficial or detrimental. We begin this review by briefly considering the multiple functi...

Mismatch Repair in Bacteria and Eukaryotes Mismatch repair in the bacterium Escherichia coli is initiated when a homodimer of MutS binds as an asymmetric clamp to DNA containing a variety of base-base and insertion-deletion mismatches. The MutL homodimer then couples MutS recognition to the signal that distinguishes between the template and nascent DNA strands. In E. coli, the lack of adenine m...