Six different base-pair transversion mismatches are repaired with different efficiencies in an in vitro mismatch repair system. In particular, the TIT and C/C mismatches appear to be less efficiently repaired than the A/A and G/G mismatches. Four A/G and four C/T mismatches at different positions are repaired to different extents. One of the A/G mismatches is repaired equally efficiently when D...

Dear Editor, Lynch syndrome (LS) is caused by a germline mutation in one of the mismatch repair (MMR) genes. Individuals with LS have an increased risk developing colorectal and many other tumours including skin tumours.1 Sebaceous neoplasms keratoacanthomas are associated LS, also known as Muir-Torre syndrome. For cutaneous squamous cell carcinoma (SCC), association has been suggested.

The process of post-replicative DNA-mismatch repair seems to be highly evolutionarily conserved. In Escherichia coli, DNA mismatches are recognized by the MutS protein. Homologues of the E. coli mutS and mutL mismatch-repair genes have been identified in other prokaryotes, as well as in yeast and mammals. Recombinant Saccharomyces cerevisiae MSH2 (MSH for MutS homologue) and human hMSH2 protein...

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...

Human cancers exhibit genomic instability and an increased mutation rate due to underlying defects in DNA repair genes. Hypermethylation of CpG islands in gene promoter regions is an important mechanism of gene inactivation in cancer. Many cellular pathways, including DNA repair, are inactivated by this type of epigenetic lesion, resulting in mutator pathways. In this review, we discuss the adv...

Colorectal cancer is undoubtedly one of the most genetically studied malignancies. In the past 20 years, substantial progress has been made in understanding the genetic and molecular pathogenesis of this cancer. It is instructive that the genes involved in the inherited colon cancer syndromes are the same genes involved in the etiology of most colorectal cancers. Familial adenomatous polyposis ...

Homonucleotide runs in coding sequences are hot spots for frameshift mutations and potential sources of genetic changes leading to cancer in humans having a mismatch repair defect. We examined frameshift mutations in homonucleotide runs of deoxyadenosines ranging from 4 to 14 bases at the same position in the LYS2 gene of the yeast Saccharomyces cerevisiae. In the msh2 mismatch repair mutant, r...