scholarly journals DNA Mismatch Repair in Eukaryotes and Bacteria

2010 ◽  
Vol 2010 ◽  
pp. 1-16 ◽  
Author(s):  
Kenji Fukui
Keyword(s):  
Mismatch Repair ◽  
Molecular Mechanisms ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Mismatch ◽  
Replication Errors ◽  
Colon Cancers ◽  
Basic Features ◽  
Almost All ◽  
Dna Replication Errors

DNA mismatch repair (MMR) corrects mismatched base pairs mainly caused by DNA replication errors. The fundamental mechanisms and proteins involved in the early reactions of MMR are highly conserved in almost all organisms ranging from bacteria to human. The significance of this repair system is also indicated by the fact that defects in MMR cause human hereditary nonpolyposis colon cancers as well as sporadic tumors. To date, 2 types of MMRs are known: the human type andEscherichia colitype. The basic features of the former system are expected to be universal among the vast majority of organisms including most bacteria. Here, I review the molecular mechanisms of eukaryotic and bacterial MMR, emphasizing on the similarities between them.

Functional consequences of DNA mismatch repair missense mutations in murine models and their impact on cancer predisposition

2005 ◽  
Vol 33 (4) ◽  
pp. 689-693 ◽  
Author(s):  
S.J. Scherer ◽  
E. Avdievich ◽  
W. Edelmann
Keyword(s):  
Mismatch Repair ◽  
Genome Stability ◽  
Dna Mismatch Repair ◽  
Significant Proportion ◽  
Missense Mutations ◽  
Dna Mismatch ◽  
Replication Errors ◽  
Tumour Suppression ◽  
Functional Consequences ◽  
Dna Replication Errors

Mutations in MMR (DNA mismatch repair) genes underlie HNPCC (hereditary non-polyposis colon cancer) and also a significant proportion of sporadic colorectal cancers. MMR maintains genome stability and suppresses tumour formation by correcting DNA replication errors and by mediating an apoptotic response to DNA damage. Analysis of mouse lines with MMR missense mutations demonstrates that these MMR functions can be separated and allows the assessment of their individual roles in tumour suppression. These studies in mice indicate that, although the increased mutation rates caused by MMR defects are sufficient to drive tumorigenesis, both functions co-operate in tumour suppression.

scholarly journals The unstructured linker arms of MutL enable GATC site incision beyond roadblocks during initiation of DNA mismatch repair

2019 ◽  
Vol 47 (22) ◽  
pp. 11667-11680 ◽  
Author(s):  
Yannicka S N Mardenborough ◽  
Katerina Nitsenko ◽  
Charlie Laffeber ◽  
Camille Duboc ◽  
Enes Sahin ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Single Molecule ◽  
Genome Stability ◽  
Dna Mismatch Repair ◽  
Dna Mismatch ◽  
Replication Errors ◽  
Dna Backbone ◽  
Dna Strand ◽  
Dna Replication Errors ◽  
Gatc Site

Abstract DNA mismatch repair (MMR) maintains genome stability through repair of DNA replication errors. In Escherichia coli, initiation of MMR involves recognition of the mismatch by MutS, recruitment of MutL, activation of endonuclease MutH and DNA strand incision at a hemimethylated GATC site. Here, we studied the mechanism of communication that couples mismatch recognition to daughter strand incision. We investigated the effect of catalytically-deficient Cas9 as well as stalled RNA polymerase as roadblocks placed on DNA in between the mismatch and GATC site in ensemble and single molecule nanomanipulation incision assays. The MMR proteins were observed to incise GATC sites beyond a roadblock, albeit with reduced efficiency. This residual incision is completely abolished upon shortening the disordered linker regions of MutL. These results indicate that roadblock bypass can be fully attributed to the long, disordered linker regions in MutL and establish that communication during MMR initiation occurs along the DNA backbone.

scholarly journals The unstructured linker arms of MutL enable GATC site incision beyond roadblocks during initiation of DNA mismatch repair

2018 ◽  
Author(s):  
Yannicka SN Mardenborough ◽  
Katerina Nitsenko ◽  
Charlie Laffeber ◽  
Camille Duboc ◽  
Enes Sahin ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Single Molecule ◽  
Genome Stability ◽  
Dna Mismatch Repair ◽  
Dna Mismatch ◽  
Replication Errors ◽  
Dna Backbone ◽  
Dna Strand ◽  
Dna Replication Errors ◽  
Gatc Site

AbstractDNA mismatch repair (MMR) maintains genome stability through repair of DNA replication errors. In Escherichia coli, initiation of MMR involves recognition of the mismatch by MutS, recruitment of MutL, activation of endonuclease MutH and DNA strand incision at a hemimethylated GATC site. Here we studied the mechanism of communication that couples mismatch recognition to daughter strand incision. We investigated the effect of catalytically-deficient Cas9 as well as stalled RNA polymerase as roadblocks placed on DNA in between the mismatch and GATC site in ensemble and single molecule nanomanipulation incision assays. The MMR proteins were observed to incise GATC sites beyond a roadblock, albeit with reduced efficiency. This residual incision is completely abolished upon shortening the disordered linker regions of MutL. These results indicate that roadblock bypass can be fully attributed to the long, disordered linker regions in MutL and establish that communication during MMR initiation occurs along the DNA backbone.

Functional Specifics of the MutL Protein of the DNA Mismatch Repair System in Different Organisms

2020 ◽  
Vol 46 (6) ◽  
pp. 875-890
Author(s):  
M. V. Monakhova ◽  
M. A. Milakina ◽  
R. M. Trikin ◽  
T. S. Oretskaya ◽  
E. A. Kubareva
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System

scholarly journals Saturation of DNA Mismatch Repair and Error Catastrophe by a Base Analogue in Escherichia coli

Genetics ◽  
2002 ◽  
Vol 161 (4) ◽  
pp. 1363-1371
Author(s):  
Kazuo Negishi ◽  
David Loakes ◽  
Roel M Schaaper
Keyword(s):  
Escherichia Coli ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Mutagenic Action ◽  
Wild Type ◽  
Dna Mismatch ◽  
Cell Counts ◽  
Error Catastrophe ◽  
Mismatch Repair System

Abstract Deoxyribosyl-dihydropyrimido[4,5-c][1,2]oxazin-7-one (dP) is a potent mutagenic deoxycytidine-derived base analogue capable of pairing with both A and G, thereby causing G · C → A · T and A · T → G · C transition mutations. We have found that the Escherichia coli DNA mismatch-repair system can protect cells against this mutagenic action. At a low dose, dP is much more mutagenic in mismatch-repair-defective mutH, mutL, and mutS strains than in a wild-type strain. At higher doses, the difference between the wild-type and the mutator strains becomes small, indicative of saturation of mismatch repair. Introduction of a plasmid containing the E. coli mutL+ gene significantly reduces dP-induced mutagenesis. Together, the results indicate that the mismatch-repair system can remove dP-induced replication errors, but that its capacity to remove dP-containing mismatches can readily be saturated. When cells are cultured at high dP concentration, mutant frequencies reach exceptionally high levels and viable cell counts are reduced. The observations are consistent with a hypothesis in which dP-induced cell killing and growth impairment result from excess mutations (error catastrophe), as previously observed spontaneously in proofreading-deficient mutD (dnaQ) strains.

scholarly journals Steady-state regulation of the human DNA mismatch repair system.

2000 ◽  
Vol 275 (37) ◽  
pp. 29178
Author(s):  
Dong Kyung Chang ◽  
Luigi Ricciardiello ◽  
Ajay Goel ◽  
Christina L. Chang ◽  
C. Richard Boland
Keyword(s):  
Steady State ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
State Regulation ◽  
Repair System ◽  
Dna Mismatch ◽  
Human Dna ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System

Oxidative stress inactivates the human DNA mismatch repair system

2002 ◽  
Vol 283 (1) ◽  
pp. C148-C154 ◽  
Author(s):  
Christina L. Chang ◽  
Giancarlo Marra ◽  
Dharam P. Chauhan ◽  
Hannah T. Ha ◽  
Dong K. Chang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mismatch Repair ◽  
Chronic Inflammation ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Microsatellites ◽  
Single Base ◽  
Dna Mismatch ◽  
Human Dna ◽  
Dna Mismatch Repair System

In the human DNA mismatch repair (MMR) system, hMSH2 forms the hMutSα and hMutSβ complexes with hMSH6 and hMSH3, respectively, whereas hMLH1 and hPMS2 form the hMutLα heterodimer. These complexes, together with other components in the MMR system, correct single-base mismatches and small insertion/deletion loops that occur during DNA replication. Microsatellite instability (MSI) occurs when the loops in DNA microsatellites are not corrected because of a malfunctioning MMR system. Low-frequency MSI (MSI-L) is seen in some chronically inflamed tissues in the absence of genetic inactivation of the MMR system. We hypothesize that oxidative stress associated with chronic inflammation might damage protein components of the MMR system, leading to its functional inactivation. In this study, we demonstrate that noncytotoxic levels of H2O2 inactivate both single-base mismatch and loop repair activities of the MMR system in a dose-dependent fashion. On the basis of in vitro complementation assays using recombinant MMR proteins, we show that this inactivation is most likely due to oxidative damage to hMutSα, hMutSβ, and hMutLα protein complexes. We speculate that inactivation of the MMR function in response to oxidative stress may be responsible for the MSI-L seen in nonneoplastic and cancer tissues associated with chronic inflammation.

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