Fig. 1.A. Mechanism of DNA mismatch repair (MMR). There are five key MMR proteins in mammalian cells including MSH2, MSH3, MSH6, MLH1, and PMS2. These proteins form heterodimer complexes to recognize and correct erroneous insertion, deletion, and misincorporation of bases that arise during ...
This article provides an overview of the MMR mechanism in mammalian cells, focusing on factors required for mismatch recognition and downstream steps, and interactions with the DNA replication machinery.ELSEVIEREncyclopedia of Biological Chemistry
DNA mismatch repair detects and removes mismatches from DNA by a conserved mechanism, reducing the error rate of DNA replication by 100- to 1,000-fold. In this process, MutS homologs scan DNA, recognize mismatches and initiate repair. How the MutS homologs selectively license repair of a mismat...
The yeast MSH2-MSH6 complex is required to repair both base-pair and single base insertion/deletion mismatches. MSH2-MSH6 binds to mismatch substrates and displays an ATPase activity that is modulated by mispairs that are repaired in vivo. To understand early steps in mismatch repair, we analyze...
The process of mismatch recognition and initiation of repair has been defined into a series of steps that have been characterized biochemically. In these separate steps it is clear that MutS, MutL and DNA go through substantial conformational changes, but so far it has not been possible to ...
Discussion This study provides genetic and biological evidence that establish the existence of a DNA repair system that mimics the canonical MutS–MutL-based MMR pathway. To date, the correction of mismatched nucleobases has been defined as a highly conserved mechanism whose key steps are performed,...
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A considerable surge of interest in the mismatch repair (MMR) system has been brought about by the discovery of a link between Lynch syndrome, an inherited predisposition to cancer of the colon and other organs, and malfunction of this key DNA metabolic pathway. This review focuses on recent ...
New insights into the mechanism of DNA mismatch repair Chromosoma (April 11, 2015), 10.1007/s00412-015-0514-0 [44] C.C. Huang, J.E. Hearst, B.M. Alberts Two types of replication proteins increase the rate at which T4 DNA polymerase traverses the helical regions in a single-stranded ...
Shared core proteins are identified as key players in both pathways, broadening the concept of DNA repair mechanism exclusivity in specific tumor types. These observations may result in unexplored forms of synthetic lethality or hypermutable tumor phenotypes, potentially impacting the cancer risk ...