Dna Mismatch Repair

Kunkel, Thomas A.; Erie, Dorothy A.

doi:10.1146/annurev.biochem.74.082803.133243

Cited by 1,215 publications

(1,342 citation statements)

References 186 publications

(299 reference statements)

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“…To this end, we designed an rpsL ‐directed ss‐oligonucleotide (SR) whose strand invasion would result in the rpsL K43T missense mutation, a P. putida analogue of the K42T mutation in E. coli (Timms et al ., 1992). SR was designed to produce a single‐base‐pair mismatch poorly detected by MMR machinery (Babic et al ., 1996; Kunkel and Erie, 2005); schemata of the K43T mutation and its targeted disruption to P. putida rpsL appear in Fig. 1B.…”

Section: Resultsmentioning

confidence: 99%

A standardized workflow for surveying recombinases expands bacterial genome‐editing capabilities

Ricaurte

Martínez‐García

Nyerges

et al. 2017

Microbial Biotechnology

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SummaryBacterial recombineering typically relies on genomic incorporation of synthetic oligonucleotides as mediated by Escherichia coli λ phage recombinase β – an occurrence largely limited to enterobacterial strains. While a handful of similar recombinases have been documented, recombineering efficiencies usually fall short of expectations for practical use. In this work, we aimed to find an efficient Recβ homologue demonstrating activity in model soil bacterium Pseudomonas putida EM42. To this end, a genus‐wide protein survey was conducted to identify putative recombinase candidates for study. Selected novel proteins were assayed in a standardized test to reveal their ability to introduce the K43T substitution into the rpsL gene of P. putida. An ERF superfamily protein, here termed Rec2, exhibited activity eightfold greater than that of the previous leading recombinase. To bolster these results, we demonstrated Rec2 ability to enter a range of mutations into the pyrF gene of P. putida at similar frequencies. Our results not only confirm the utility of Rec2 as a Recβ functional analogue within the P. putida model system, but also set a complete workflow for deploying recombineering in other bacterial strains/species. Implications range from genome editing of P. putida for metabolic engineering to extended applications within other Pseudomonads – and beyond.

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Section: Resultsmentioning

confidence: 99%

A standardized workflow for surveying recombinases expands bacterial genome‐editing capabilities

Ricaurte

Martínez‐García

Nyerges

et al. 2017

Microbial Biotechnology

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“…In Escherichia coli, the methyl-directed MMR system has been extensively studied, and the entire pathway has been reconstituted in vitro from purified proteins in the Modrich laboratory (Table 1, reviewed in Kunkel and Erie, 2005;Schofield and Hsieh, 2003). MMR in prokaryotes is initiated when mismatches are recognized by a highly conserved MMR protein, MutS.…”

Section: Mutation Avoidance and Post-replication Repairmentioning

confidence: 99%

“…First, whereas bacterial MutS and MutL proteins function as homodimeric proteins, their eukaryotic counterparts are invariably heterodimers composed of two related, but distinct protein subunits. In fact, eukaryotic cells possess several MutS and MutL homologues, and the choice of subunit partner dictates substrate specificity and cellular function (see Table 1; Kunkel and Erie, 2005). MSH2-MSH6, or MutSα, targets base-base mispairs and +1 IDLs; MSH2-MSH3, or MutSβ, targets primarily IDLs though recent genetic and biochemical data support a role for yMsh3 in the repair of certain base-base mispairs in vivo (Harrington and Kolodner, 2007).…”

Section: Mutation Avoidance and Post-replication Repairmentioning

confidence: 99%

“…Since discrimination between mismatched DNA and perfectly paired DNA is not large, most commonly no more than two orders of magnitude (reviewed in Jiricny, 2006;Kunkel and Erie, 2005;Schofield and Hsieh, 2003), the issue of finding a mismatch is not trivial. Total internal reflection fluorescence microscopy of yMSH2-MSH6 reveals that the protein travels along undamaged DNA duplexes via ID diffusion (Gorman et al, 2007).…”

Section: Mutation Avoidance and Post-replication Repairmentioning

confidence: 99%

“…We review what is known concerning the molecular mechanism of MMR, its role in DNA damage signalling, and its relationship to cancer and ageing. The recent literature is emphasized; for more comprehensive discussions, please see Harfe and Jinks-Robertson (2000), Jiricny (2006), Kunkel and Erie (2005), Modrich (2006), Schofield and Hsieh (2003).…”

Section: Introductionmentioning

confidence: 99%

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DNA mismatch repair: Molecular mechanism, cancer, and ageing

Hsieh

Yamane

2008

Mechanisms of Ageing and Development

397

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DNA mismatch repair (MMR) proteins are ubiquitous players in a diverse array of important cellular functions. In its role in post-replication repair, MMR safeguards the genome correcting base mispairs arising as a result of replication errors. Loss of MMR results in greatly increased rates of spontaneous mutation in organisms ranging from bacteria to humans. Mutations in MMR genes cause hereditary nonpolyposis colorectal cancer, and loss of MMR is associated with a significant fraction of sporadic cancers. Given its prominence in mutation avoidance and its ability to target a range of DNA lesions, MMR has been under investigation in studies of ageing mechanisms. 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.

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In Vitro Antibacterial Resistance Selection and Quantitation

Young

2006

CP Pharmacology

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The study of resistance is vital to the discovery and development of new antibacterial agents. Consider the case where the resistance frequency (the proportion of cells within a population that exhibit a resistance phenotype to the agent under study) of an agent is such that, in an average infection, a mutant resistant to the agent is likely to already exist. This compound will not be useful in the clinic as a single agent, since this mutant can survive its administration, leading to potential clinical failure. This unit provides protocols for determining the frequency and rate of resistance to antibacterial agents, as well as generating resistant mutants for mechanism of action determinations or for use in antibacterial discovery or development programs.

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Dna Mismatch Repair

Cited by 1,215 publications

References 186 publications

A standardized workflow for surveying recombinases expands bacterial genome‐editing capabilities

A standardized workflow for surveying recombinases expands bacterial genome‐editing capabilities

DNA mismatch repair: Molecular mechanism, cancer, and ageing

In Vitro Antibacterial Resistance Selection and Quantitation

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