SnapShot: DNA Mismatch Repair

  title={SnapShot: DNA Mismatch Repair},
  author={Andres A. Larrea and Scott A Lujan and Thomas A Kunkel},
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 methylation, catalyzed by the DNA adenine methyltransferase (Dam) in newly synthesized GATC sequences… 
Mismatch repair causes the dynamic release of an essential DNA polymerase from the replication fork
It is proposed that MutS directly contacts the DNA replication machinery, causing a dynamic change in the organization of DnaE at the replication fork during MMR, establishing a striking and intimate connection between MMR and the replicating DNA polymerase complex in vivo.
DnaN clamp zones provide a platform for spatiotemporal coupling of mismatch detection to DNA replication
The role of the Bacillus subtilis processivity clamp DnaN is investigated, and it is found that it serves as a platform for mismatch detection and coupling of repair to DNA replication.
Synergism of Dam, MutH, and MutS in methylation-directed mismatch repair in Escherichia coli.
Interestingly, double defects in dam and mutS synergistically produced a dramatically higher spontaneous mutation frequency than the summation of mutation frequencies of FX-11 strains with individual deficiency of dam or mutS, suggesting that Dam may work with MutHL to partially accomplish the task of recognizing the mismatch sites to retain partial mismatch repair capacity.
The role of Bacillus anthracis RecD2 helicase in DNA mismatch repair.
This work used papillation as a tool to search for B. anthracis new mutator strains and identified a spontaneous mutator that carries a minitransposon insertion in the BAS4289 locus, the first report of a RecD2 helicase being associated with MMR.
Chemical Trapping of the Dynamic MutS-MutL Complex Formed in DNA Mismatch Repair in Escherichia coli*
Chemical cross-linking and fluorescence resonance energy transfer is used to study the interaction between MutS and MutL and to shed light onto the structure of this dynamic complex and identify the structural features of key events in DNA mismatch repair.
The C-Terminal Domain of the MutL Homolog from Neisseria gonorrhoeae Forms an Inverted Homodimer
The crystal structure of the C-terminal domain (CTD) of the MutL homolog of Neisseria gonorrhoeae (NgoL) determined to a resolution of 2.4 Å shows that the metal binding motif exists in a helical configuration and that four of the six conserved motifs in theMutL family, including the metalbinding site, localize together to form a composite active site.
Control of Genome Stability by EndoMS/NucS-Mediated Non-Canonical Mismatch Repair
A further understanding of the EndoMS/NucS-mediated non-canonical mismatch repair (MMR) pathway may reveal new strategies to predict and fight drug resistance.
DNA mismatch repair enzymes: genetic defects and autoimmunity.
The functional structures ofMMREs, their genetic defects and associated disorders, and autoimmunity to MMREs are charted, including the recent data that was the first to analyze autoantibodies against all seven kinds of MM REs in systemic autoimmune diseases, including idiopathic inflammatory myopathies.
Trapping and visualizing intermediate steps in the mismatch repair pathway in vivo
A discrete site on MutS that is occupied by MutL in Bacillus subtilis is identified, providing insights into the mechanism that MutS employs to recruit MutL, and the consequences that ensue when MutL recruitment is blocked.
DNA Repair Polymerases
This review focuses on the role of the numerous prokaryotic and eukaryotic DNA polymerases identified to date in the major DNA repair pathways: base excision repair (BER), nucleotide excision repaired (NER), doublestrand break repair (DSBR), cross-link repair (CLR), and mismatch repair (MMR).


A possible mechanism for exonuclease 1-independent eukaryotic mismatch repair
A mechanism may account, at least in part, for the Exo1-independent repair that occurs in eukaryotic cells, and hence the modest cancer predisposition of Exo 1-deficient mammalian cells.
MutS mediates heteroduplex loop formation by a translocation mechanism
Observations suggest a translocation mechanism in which a MutS dimer bound to a mismatch subsequently leaves this site by ATP‐dependent tracking or unidimensional movement that is in most cases bidirectional from the mispair.
Mechanisms and functions of DNA mismatch repair
Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including hereditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.
DNA mismatch repair and genetic instability.
The genetic and biochemical approaches used to study MMR are described, and the diverse roles that MMR proteins play in maintaining genetic stability are summarized.
DNA mismatch repair.
This review focuses on the biochemical mechanism of MMR replication errors, on structure-function studies of MMR proteins, on how mismatches are recognized, on the process by which the newly replicated strand is identified, and on excision of the replication error.
The coordinated functions of the E. coli MutS and MutL proteins in mismatch repair.
A model of MMR that relies on two dynamic and redundant ATP-regulated molecular switches is supported, based on biochemical and genetic studies to ascertain a physiologically relevant mechanism for MMR.
Eukaryotic DNA mismatch repair.
Eukaryotic mismatch repair (MMR) has been shown to require two different heterodimeric complexes of MutS-related proteins: MSH 2-MSH3 and MSH2- MSH6, and alternative models have been proposed for how these MSH complexes function in MMR.
The origins and early evolution of DNA mismatch repair genes—multiple horizontal gene transfers and co-evolution
An overall portrait of the evolution of these important genes in DNA metabolism is presented, indicating that not only archaea, but also bacteria are important sources of eukaryotic DNA metabolic genes.
DNA mismatch repair: Molecular mechanism, cancer, and ageing
This review summarizes what is known about the molecular details of the MMR pathway and the role of MMR proteins in cancer susceptibility and ageing.