Characterization of the defects in the ATP lid of E. coli MutL that cause transient hypermutability

Pillon, Monica C.; Dubinsky, Michelle K.; Johnston, Randal N.; Liu, Shulin; Guarné, Alba

doi:10.1016/j.dnarep.2013.07.003

Cited by 5 publications

(3 citation statements)

References 40 publications

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“…Mutations in the ATPase domain of hMutLα abolish the ATP hydrolytic activity of hMutLα [16]. ATP hydrolysis is indispensable for hMutLα activity in MMR, and mutant hMutLα lacks the MMR activity, indicating the important function of hMutLα ATP hydrolysis in MMR, which is consistent with studies of MutL in E.coli [17–19]. In Lynch syndrome, missense mutations in or near the ATP binding site confer increased mutagenesis, perhaps due to diminished ATP hydrolysis [17].…”

Section: Introductionsupporting

confidence: 80%

The MLH1 ATPase domain is needed for suppressing aberrant formation of interstitial telomeric sequences

Jia

Chai

2018

DNA Repair

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Genome instability gives rise to cancer. MLH1, commonly known for its important role in mismatch repair (MMR), DNA damage signaling and double-strand break (DSB) repair, safeguards genome stability. Recently we have reported a novel role of MLH1 in preventing aberrant formation of interstitial telomeric sequences (ITSs) at intra-chromosomal regions. Deficiency in MLH1, in particular its N-terminus, leads to an increase of ITSs. Here, we identify that the ATPase activity in the MLH1 N-terminal domain is important for suppressing the formation of ITSs. The ATPase activity is also needed for recruiting MLH1 to DSBs. Moreover, defective ATPase activity of MLH1 causes an increase in micronuclei formation. Our results highlight the crucial role of MLH1's ATPase domain in preventing the aberrant formation of telomeric sequences at the intra-chromosomal regions and preserving genome stability.

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Section: Introductionsupporting

confidence: 80%

The MLH1 ATPase domain is needed for suppressing aberrant formation of interstitial telomeric sequences

Jia

Chai

2018

DNA Repair

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“…Overall, these results motivate the conclusion that increased mutation rates rapidly evolved in these populations. Notably, a previous study found that addition or subtraction of the LA repeat in the LALALA motif of MutL impairs the ATP-binding function critical for DNA mismatch repair 27 .…”

Section: Resultsmentioning

confidence: 99%

Rapid evolution of mutation rate and spectrum in response to environmental and population-genetic challenges

Wang

Behringer

et al. 2022

Nat Commun

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Ecological and demographic factors can significantly shape the evolution of microbial populations both directly and indirectly, as when changes in the effective population size affect the efficiency of natural selection on the mutation rate. However, it remains unclear how rapidly the mutation-rate responds evolutionarily to the entanglement of ecological and population-genetic factors over time. Here, we directly assess the mutation rate and spectrum of Escherichia coli clones isolated from populations evolving in response to 1000 days of different transfer volumes and resource-replenishment intervals. The evolution of mutation rates proceeded rapidly in response to demographic and/or environmental changes, with substantial bidirectional shifts observed as early as 59 generations. These results highlight the remarkable rapidity by which mutation rates are shaped in asexual lineages in response to environmental and population-genetic forces, and are broadly consistent with the drift-barrier hypothesis for the evolution of mutation rates, while also highlighting situations in which mutator genotypes may be promoted by positive selection.

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“…And then the molecular matchmaker MutL was recruited in an ATP-dependent manner, while the MutS recognizes and binds to a mismatch (Junop et al, 2001). Several studies have linked the conserved short tandem repeat with the MutL (Pillon et al, 2013). The lack of a mismatch repairing system may facilitate intra-chromosomal exchanges between tandemrepeated and interspersed sequences in the genome of M. tuberculosis (Springer et al, 2004).…”

Section: Mechanisms Of Vntr Sequence Variationmentioning

confidence: 99%

The discovery, function and development of the variable number tandem repeats in differentMycobacteriumspecies

Sun

Liu

et al. 2015

Critical Reviews in Microbiology

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The method of genotyping by variable number tandem repeats (VNTRs) facilitates the epidemiological studies of different Mycobacterium species worldwide. Until now, the VNTR method is not fully understood, for example, its discovery, function and classification. The inconsistent nomenclature and terminology of VNTR is especially confusing. In this review, we first describe in detail the VNTRs in Mycobacterium tuberculosis (M. tuberculosis), as this pathogen resulted in more deaths than any other microbial pathogen as well as for which extensive studies of VNTRs were carried out, and then we outline the recent progress of the VNTR-related epidemiological research in several other Mycobacterium species, such as M. abscessus, M. africanum, M. avium, M. bovis, M. canettii, M. caprae, M. intracellulare, M. leprae, M. marinum, M. microti, M. pinnipedii and M. ulcerans from different countries and regions. This article is aimed mainly at the practical notes of VNTR to help the scientists in better understanding and performing this method.

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Characterization of the defects in the ATP lid of E. coli MutL that cause transient hypermutability

Cited by 5 publications

References 40 publications

The MLH1 ATPase domain is needed for suppressing aberrant formation of interstitial telomeric sequences

The MLH1 ATPase domain is needed for suppressing aberrant formation of interstitial telomeric sequences

Rapid evolution of mutation rate and spectrum in response to environmental and population-genetic challenges

The discovery, function and development of the variable number tandem repeats in differentMycobacteriumspecies

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