The
            <i>Escherichia coli</i>
            Mismatch Repair Protein MutL Recruits the Vsr and MutH Endonucleases in Response to DNA Damage

Polosina, Yaroslava Y.; Mui, Justin; Pitsikas, Photini; Cupples, Claire G.

doi:10.1128/jb.00066-09

Cited by 12 publications

(11 citation statements)

References 24 publications

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“…MutH and Vsr are recruited to sites of DNA damage by MutL and MutS, regardless of their ability to participate in the repair of the lesion. (41) Since MutL levels do not change during the cell cycle, (42,43) the choice of endonuclease probably depends on relative abundance. The level of MutH is high in dividing cells and low in stationary phase; (42) this and the transience of hemimethylation restrict MMR to dividing cells.…”

Section: Post-replication Mismatch Repair: the Standard Repertoirementioning

confidence: 99%

MutL: conducting the cell's response to mismatched and misaligned DNA

Polosina

Cupples

2009

BioEssays

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Base pair mismatches in DNA arise from errors in DNA replication, recombination, and biochemical modification of bases. Mismatches are inherently transient. They are resolved passively by DNA replication, or actively by enzymatic removal and resynthesis of one of the bases. The first step in removal is recognition of strand discontinuity by one of the MutS proteins. Mismatches arising from errors in DNA replication are repaired in favor of the base on the template strand, but other mismatches trigger base excision or nucleotide excision repair (NER), or non-repair pathways such as hypermutation, cell cycle arrest, or apoptosis. We argue that MutL homologues play a key role in determining biologic outcome by recruiting and/or activating effector proteins in response to lesion recognition by MutS. We suggest that the process is regulated by conformational changes in MutL caused by cycles of ATP binding and hydrolysis, and by physiologic changes which influence effector availability.

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Section: Post-replication Mismatch Repair: the Standard Repertoirementioning

confidence: 99%

MutL: conducting the cell's response to mismatched and misaligned DNA

Polosina

Cupples

2009

BioEssays

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“…Key to this process is the temperature-controlled expression of a dominantnegative mutator allele of the E. coli MMR protein MutL (20), enabling transient suppression of DNA repair during oligonucleotide integration. MutL is a component of the MutHLS complex responsible for methyl-directed mismatch repair, acting to recruit the MutH endonuclease to sites of DNA damage (21). Importantly, this particular mutator allele cannot be complemented by the native MutL protein (20).…”

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confidence: 99%

A highly precise and portable genome engineering method allows comparison of mutational effects across bacterial species

Nyerges

Csörgő

Nagy

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

200

256

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Currently available tools for multiplex bacterial genome engineering are optimized for a few laboratory model strains, demand extensive prior modification of the host strain, and lead to the accumulation of numerous off-target modifications. Building on prior development of multiplex automated genome engineering (MAGE), our work addresses these problems in a single framework. Using a dominant-negative mutant protein of the methyl-directed mismatch repair (MMR) system, we achieved a transient suppression of DNA repair in Escherichia coli, which is necessary for efficient oligonucleotide integration. By integrating all necessary components into a broad-host vector, we developed a new workflow we term pORTMAGE. It allows efficient modification of multiple loci, without any observable off-target mutagenesis and prior modification of the host genome. Because of the conserved nature of the bacterial MMR system, pORTMAGE simultaneously allows genome editing and mutant library generation in other biotechnologically and clinically relevant bacterial species. Finally, we applied pORTMAGE to study a set of antibiotic resistance-conferring mutations in Salmonella enterica and E. coli. Despite over 100 million y of divergence between the two species, mutational effects remained generally conserved. In sum, a single transformation of a pORTMAGE plasmid allows bacterial species of interest to become an efficient host for genome engineering. These advances pave the way toward biotechnological and therapeutic applications. Finally, pORTMAGE allows systematic comparison of mutational effects and epistasis across a wide range of bacterial species.genome engineering | synthetic biology | recombineering | off-target effects | methyl-directed mismatch repair

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“…MutL has been shown to stimulate the nicking reaction catalyzed by the Vsr endonuclease (24,32,35). Therefore, it is possible that MutL is able to increase the efficiency of VSP repair by stimulating the nicking reaction catalyzed by the Vsr endonuclease.…”

Section: Discussionmentioning

confidence: 99%

“…8. MutS binds to the T:G mis- (24,35); other protein-protein interactions, if they exist, are hypothetical. The Vsr endonuclease catalyzes the hydrolysis of a phosphodiester bond 5Ј to the mismatched thymidine.…”

Section: Discussionmentioning

confidence: 99%

“…This nick translation reaction leaves a ligatable nick that is presumably sealed by DNA ligase I to restore the integrity of the E. coli genome. The exact functions of MutL and MutS in the pathway remain unknown, although MutL has been suggested to stimulate the activity of the Vsr endonuclease (32,35). Unlike methyl-directed mismatch repair, deletion of MutS or MutL does not abolish the activity of the VSP repair pathway.…”

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confidence: 99%

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Reconstitution of the Very Short Patch Repair Pathway from Escherichia coli

Robertson

Matson

2012

Journal of Biological Chemistry

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Background: Very short patch repair rectifies thymidine-guanine mismatches arising from spontaneous deamination of 5-methyl cytosine. Results: The very short patch repair pathway was reconstituted using purified enzymes. Conclusion: Patch length depends on the concentration of DNA ligase and may be regulated by the addition of MutS and MutL. Significance: The results suggest roles for MutL and MutS in very short patch repair.

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The Escherichia coli Mismatch Repair Protein MutL Recruits the Vsr and MutH Endonucleases in Response to DNA Damage

Cited by 12 publications

References 24 publications

MutL: conducting the cell's response to mismatched and misaligned DNA

MutL: conducting the cell's response to mismatched and misaligned DNA

A highly precise and portable genome engineering method allows comparison of mutational effects across bacterial species

Reconstitution of the Very Short Patch Repair Pathway from Escherichia coli

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