The mammalian ortholog of yeast Slx4, BTBD12, is an ATM substrate that functions as a scaffold for various DNA repair activities. Mutations of human BTBD12 have been reported in a new sub-type of Fanconi anemia patients. Recent studies have implicated the fly and worm orthologs, MUS312 and HIM-18, in the regulation of meiotic crossovers arising from double-strand break (DSB) initiating events a...

CAG/CTG repeats are structure-forming repetitive DNA sequences, and expansion beyond a threshold of ∼35 CAG repeats is the cause of several human diseases. Expanded CAG repeats are prone to breakage, and repair of the breaks can cause repeat contractions and expansions. In this study, we found that cotranscriptional R-loops formed at a CAG-70 repeat inserted into a yeast chromosome. R-loops wer...

Hereditary non-polyposis colorectal cancer (HNPCC) syndrome is a dominantly inherited condition, recognised by Lynch et al in 1966, associated with a major susceptibility to colorectal and endometrial cancer. The use of stringent criteria in the definition of the syndrome led to the initial identification of two genes, MSH2 and MLH1, which when mutated are responsible for the cancer susceptibil...

Abstract Background Patients carried defects on cancer susceptibility genes or had family history have at least twice the risk of developing than general population, with both early onset and multiple cancers features. For elucidating carrier rate in patients inherited colorectal (CRC) endometrial (EnCa) Taiwan, we established a NCCN guided 30-gene panel which included four DNA Mismatch Repair ...

Methyl-directed mismatch repair is a coordinated process that ensures replication fidelity and genome integrity by resolving base pair mismatches and insertion/deletion loops. This post-replicative event involves the activities of several proteins, many of which appear to be regulated by MutL. MutL interacts with and modulates the activities of MutS, MutH, UvrD, and perhaps other proteins. The ...

The methylation of CpG islands in the promoters is associated with loss of protein via repression of gene transcription. Several studies have demonstrated that tumour suppressor and DNA repair genes are often aberrantly hypermethylated in colorectal cancer. The present study was conducted to examine whether the methylation profile of p16INK4a and hMLH1 (human mutL homologue 1) promoters was ass...

sequences (recently reviewed in Buermeyer et al., 1999; Kolodner and Marsischky, 1999; Harfe and Jinks-Robertson, 2000; Hsieh, 2001). In the most thoroughly characterized Escherichia coli MMR system, which serves as a paradigm for eukaryotic MMR studies, initiation of MMR requires the products of mutS, mutL and mutH genes. A homodimer of MutS binds to mismatches in DNA and a homodimer of MutL c...

B efore meiotic divisions, chromosomes form crossovers, which represent the reciprocal exchanges between the DNA molecules of the homolo-gous partner chromosomes. These crossovers aren't just important for reassorting genetic traits; they're essential for the correct alignment and segregation of meiotic chromosomes. To ensure that every homologous chromosome pair forms at least one cross-over—a...

A small subset of the 200–300 double-strand breaks (DSBs) formed during early prophase of meiosis I in mouse spermatocytes is used to generate a highly regulated number of meiotic crossovers (COs; 20–30), with the excess DSBs being repaired as non-COs. The progressive differentiation process during prophase I that leads to CO formation can be observed cytologically by immunolocalization of cons...

Meiotic recombination is essential for the production of viable haploid gametes in sexually-reproducing organisms, and creates new allelic combinations, whichmay facilitate evolution by natural selection and genetic drift (Barton & Charlesworth, 1998). Crossovers between homologous chromosomes establish physical connections (chiasmata) which enable proper chromosome segregation. In the absence ...