scholarly journals An Induced Mutation in HvRECQL4 Increases the Overall Recombination and Restores Fertility in a Barley HvMLH3 Mutant Background

2021 ◽  
Vol 12 ◽  
Author(s):  
Mikel Arrieta ◽  
Malcolm Macaulay ◽  
Isabelle Colas ◽  
Miriam Schreiber ◽  
Paul D. Shaw ◽  
...  
Keyword(s):  
Crop Improvement ◽  
Low Frequency ◽  
Crossing Over ◽  
Target Sequence ◽  
Helicase Domain ◽  
Dna Mismatch ◽  
Complete Restoration ◽  
Dna Mismatch Repair Genes ◽  
Restoration Of Fertility

Plant breeding relies on the meiotic recombination or crossing over to generate the new combinations of the alleles along and among the chromosomes. However, crossing over is constrained in the crops such as barley by a combination of the low frequency and biased distribution. In this study, we attempted to identify the genes that limit the recombination by performing a suppressor screen for the restoration of fertility to the semi-fertile barley mutant desynaptic10 (des10), carrying a mutation in the barley ortholog of MutL-Homolog 3 (HvMLH3), a member of the MutL-homolog (MLH) family of DNA mismatch repair genes. des10 mutants exhibit reduced recombination and fewer chiasmata, resulting in the loss of obligate crossovers (COs) leading to chromosome mis-segregation. We identified several candidate suppressor lines and confirmed their restored fertility in an Hvmlh3 background in the subsequent generations. We focus on one of the candidate suppressor lines, SuppLine2099, which showed the most complete restoration of fertility. We characterized this line by using a target-sequence enrichment and sequencing (TENSEQ) capture array representing barley orthologs of 46 meiotic genes. We found that SuppLine2099 contained a C/T change in the anti-CO gene RecQ-like helicase 4 (RECQL4) resulting in the substitution of a non-polar glycine to a polar aspartic acid (G700D) amino acid in the conserved helicase domain. Single nucleotide polymorphism (SNP) genotyping of F3 populations revealed a significant increase in the recombination frequency in lines with Hvrecql4 in the Hvmlh3 background that was associated with the restoration of fertility. The genotyping also indicated that there was nearly double the recombination levels in homozygous Hvrecql4 lines compared to the wild type (WT). However, we did not observe any significant change in the distribution of CO events. Our results confirm the anti-CO role of RECQL4 in a large genome cereal and establish the possibility of testing the utility of increasing recombination in the context of traditional crop improvement.

scholarly journals Systematic Mutagenesis of the Saccharomyces cerevisiae MLH1 Gene Reveals Distinct Roles for Mlh1p in Meiotic Crossing Over and in Vegetative and Meiotic Mismatch Repair

2003 ◽  
Vol 23 (3) ◽  
pp. 873-886 ◽  
Author(s):  
Juan Lucas Argueso ◽  
Amanda Wraith Kijas ◽  
Sumeet Sarin ◽  
Julie Heck ◽  
Marc Waase ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Ternary Complex ◽  
Genetic Recombination ◽  
Crossing Over ◽  
Wild Type ◽  
Dna Mismatch ◽  
Biochemical Assays ◽  
Postmeiotic Segregation ◽  
New Alleles

ABSTRACT In eukaryotic cells, DNA mismatch repair is initiated by a conserved family of MutS (Msh) and MutL (Mlh) homolog proteins. Mlh1 is unique among Mlh proteins because it is required in mismatch repair and for wild-type levels of crossing over during meiosis. In this study, 60 new alleles of MLH1 were examined for defects in vegetative and meiotic mismatch repair as well as in meiotic crossing over. Four alleles predicted to disrupt the Mlh1p ATPase activity conferred defects in all functions assayed. Three mutations, mlh1-2, -29, and -31, caused defects in mismatch repair during vegetative growth but allowed nearly wild-type levels of meiotic crossing over and spore viability. Surprisingly, these mutants did not accumulate high levels of postmeiotic segregation at the ARG4 recombination hotspot. In biochemical assays, Pms1p failed to copurify with mlh1-2, and two-hybrid studies indicated that this allele did not interact with Pms1p and Mlh3p but maintained wild-type interactions with Exo1p and Sgs1p. mlh1-29 and mlh1-31 did not alter the ability of Mlh1p-Pms1p to form a ternary complex with a mismatch substrate and Msh2p-Msh6p, suggesting that the region mutated in these alleles could be responsible for signaling events that take place after ternary complex formation. These results indicate that mismatches formed during genetic recombination are processed differently than during replication and that, compared to mismatch repair functions, the meiotic crossing-over role of MLH1 appears to be more resistant to mutagenesis, perhaps indicating a structural role for Mlh1p during crossing over.

scholarly journals Role of the Pathologist in the Diagnosis of Hereditary Non-Polyposis Colorectal Cancer

2004 ◽  
Vol 20 (4-5) ◽  
pp. 215-224 ◽  
Author(s):  
Jeremy R. Jass
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Tumor Infiltrating Lymphocytes ◽  
Dna Mismatch ◽  
Repair Deficiency ◽  
Dna Mismatch Repair Genes ◽  
Histological Criteria ◽  
Dna Microsatellite ◽  
Infiltrating Lymphocytes

The aim of this paper is to indicate how the pathologist may suspect a diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) on the basis of histological criteria and patient age alone. A single morphological feature, namely the presence of intra-epithelial lymphocytes (tumor infiltrating lymphocytes), identifies the majority of colorectal cancers (CRC) with the DNA microsatellite instability-high phenotype. A number of pathological criteria can help to distinguish HNPCC from sporadic MSI-H CRC, though age below 60 years is an important pointer towards HNPCC. Immunohistochemistry to demonstrate loss of expression of DNA mismatch repair genes serves as a highly reliable test of mismatch repair deficiency if antibodies to hMLH1, hMSH2, hMSH6 and hPMS2 are employed.

Role of DNA Mismatch Repair Genes in Colorectal Cancer

2021 ◽  
pp. 209-223
Author(s):  
Sonal Gupta ◽  
Manisha Mathur ◽  
Beiping Miao ◽  
Prashanth Suravajhala ◽  
Obul Reddy Bandapalli
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Mismatch Repair Genes ◽  
Dna Mismatch ◽  
Dna Mismatch Repair Genes ◽  
Repair Genes

scholarly journals Role of DNA mismatch repair genes in lung and head and neck cancer (Review)

2019 ◽  
Author(s):  
Sotirios Doukas ◽  
Dimitra Vageli ◽  
Taxiarchis Nikolouzakis ◽  
Luca Falzone ◽  
Anca Docea ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Mismatch Repair ◽  
Neck Cancer ◽  
Mismatch Repair Genes ◽  
Dna Mismatch ◽  
Cancer Review ◽  
Dna Mismatch Repair Genes ◽  
Repair Genes

Calculation-and-experimental estimation of the role of the frequency ratio in changing the endurance at two-frequency deformation modes

2019 ◽  
Vol 85 (1(I)) ◽  
pp. 64-71 ◽  
Author(s):  
M. M. Gadenin
Keyword(s):  
High Frequency ◽  
Experimental Studies ◽  
Low Frequency ◽  
Reduction Factor ◽  
Single Frequency ◽  
Cyclic Loads ◽  
Small Ratio ◽  
Harmonic Components ◽  
Deformation Modes

The cycle configuration at two-frequency loading regimes depends on the number of parameters including the absolute values of the frequencies and amplitudes of the low-frequency and high-frequency loads added during this mode, the ratio of their frequencies and amplitudes, as well as the phase shift between these harmonic components, the latter having a significant effect only with a small ratio of frequencies. Presence of such two-frequency regimes or service loading conditions for parts of machines and structures schematized by them can significantly reduce their endurance. Using the results of experimental studies of changes in the endurance of a two-frequency loading of specimens of cyclically stable, cyclically softened and cyclically hardened steels under rigid conditions we have shown that decrease in the endurance under the aforementioned conditions depends on the ratio of frequencies and amplitudes of operation low-frequency low-cycle and high-frequency vibration stresses, and, moreover, the higher the level of the ratios of amplitudes and frequencies of those stacked harmonic processes of loading the greater the effect. It is shown that estimation of such a decrease in the endurance compared to a single frequency loading equal in the total stress (strains) amplitudes can be carried out using an exponential expression coupling those endurances through a parameter (reduction factor) containing the ratio of frequencies and amplitudes of operation cyclic loads and characteristic of the material. The reduction is illustrated by a set of calculation-experimental curves on the corresponding diagrams for each of the considered types of materials and compared with the experimental data.

When to Consider Lynch Syndrome in Non-Colon and Non-Endometrial Malignancies

2021 ◽  
pp. 000313482110318
Author(s):  
Aaron J. Arroyave ◽  
Alan W. Good ◽  
Andrew J. Ward ◽  
Amila L. Orucevic ◽  
James M. McLoughlin
Keyword(s):  
Lynch Syndrome ◽  
Review Article ◽  
Genetic Syndrome ◽  
Clinical Criteria ◽  
Dna Mismatch ◽  
Dna Mismatch Repair Genes ◽  
Associated Malignancy ◽  
Revised Bethesda Guidelines ◽  
Current Guidelines ◽  
Repair Genes

Lynch syndrome (LS) is a common genetic syndrome characterized by pathogenic mutations of DNA mismatch repair genes resulting in a hereditary predisposition to cancer. While typically associated with colonic and endometrial cancer, LS additionally influences the development of many other malignancies. The Amsterdam II and Revised Bethesda Guidelines are the established clinical criteria for diagnosing LS. These guidelines are based on the most general characteristics of LS and do not address specific characteristics of the less commonly LS-associated malignancies. For individuals that present initially with a non-colon and non-endometrial malignancy, recommendations and guidelines on when to consider screening for LS are limited. Therefore, it is essential that clinicians are familiar with distinct LS-associated patient- and tumor-specific characteristics, especially of the less common LS-associated cancers, so that LS’s diagnosis is not missed. In this review article, we focus on extra-colonic and extra-endometrial LS-associated cancers, paying particular attention to any established or currently investigated cancer features that help raise suspicion for LS and potentially lead to its earlier diagnosis. This review will also discuss current guidelines specific to each LS-associated malignancy.

scholarly journals High Ripple-Density Resolution for Discriminating Between Rippled and Nonrippled Signals: Effect of Temporal Processing or Combination Products?

2021 ◽  
Vol 25 ◽  
pp. 233121652110101
Author(s):  
Dmitry I. Nechaev ◽  
Olga N. Milekhina ◽  
Marina S. Tomozova ◽  
Alexander Y. Supin
Keyword(s):  
Low Frequency ◽  
Noise Signal ◽  
Density Variation ◽  
Choice Procedure ◽  
Masker Level ◽  
Reference Signals ◽  
Forced Choice Procedure ◽  
The Mean ◽  
Density Resolution

The goal of the study was to investigate the role of combination products in the higher ripple-density resolution estimates obtained by discrimination between a spectrally rippled and a nonrippled noise signal than that obtained by discrimination between two rippled signals. To attain this goal, a noise band was used to mask the frequency band of expected low-frequency combination products. A three-alternative forced-choice procedure with adaptive ripple-density variation was used. The mean background (unmasked) ripple-density resolution was 9.8 ripples/oct for rippled reference signals and 21.8 ripples/oct for nonrippled reference signals. Low-frequency maskers reduced the ripple-density resolution. For masker levels from −10 to 10 dB re. signal, the ripple-density resolution for nonrippled reference signals was approximately twice as high as that for rippled reference signals. At a masker level as high as 20 dB re. signal, the ripple-density resolution decreased in both discrimination tasks. This result leads to the conclusion that low-frequency combination products are not responsible for the task-dependent difference in ripple-density resolution estimates.

scholarly journals NMDA Receptor-Dependent Synaptic Activity in Dorsal Motor Nucleus of Vagus Mediates the Enhancement of Gastric Motility by Stimulating ST36

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Xinyan Gao ◽  
Yongfa Qiao ◽  
Baohui Jia ◽  
Xianghong Jing ◽  
Bin Cheng ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Gastric Motility ◽  
Low Frequency ◽  
Synaptic Activity ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Vagal Reflex ◽  
Precise Molecular Mechanism ◽  
Lines Of Evidence

Previous studies have demonstrated the efficacy of electroacupuncture at ST36 for patients with gastrointestinal motility disorders. While several lines of evidence suggest that the effect may involve vagal reflex, the precise molecular mechanism underlying this process still remains unclear. Here we report that the intragastric pressure increase induced by low frequency electric stimulation at ST36 was blocked by AP-5, an antagonist of N-methyl-D-aspartate receptors (NMDARs). Indeed, stimulating ST36 enhanced NMDAR-mediated, but not 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic-acid-(AMPA-) receptor-(AMPAR-) mediated synaptic transmission in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). We also identified that suppression of presynapticμ-opioid receptors may contribute to upregulation of NMDAR-mediated synaptic transmission induced by electroacupuncture at ST36. Furthermore, we determined that the glutamate-receptor-2a-(NR2A-) containing NMDARs are essential for NMDAR-mediated enhancement of gastric motility caused by stimulating ST36. Taken together, our results reveal an important role of NMDA receptors in mediating enhancement of gastric motility induced by stimulating ST36.

scholarly journals Interaction of the Tobacco Mosaic Virus Replicase Protein with the Aux/IAA Protein PAP1/IAA26 Is Associated with Disease Development

2005 ◽  
Vol 79 (4) ◽  
pp. 2549-2558 ◽  
Author(s):  
Meenu S. Padmanabhan ◽  
Sameer P. Goregaoker ◽  
Sheetal Golem ◽  
Haiymanot Shiferaw ◽  
James N. Culver
Keyword(s):  
Tobacco Mosaic Virus ◽  
Mosaic Virus ◽  
Protein S ◽  
Helicase Domain ◽  
Auxin Response ◽  
Disease Symptoms ◽  
Developmental Abnormalities ◽  
Replicase Protein ◽  
Transcriptional Alterations

ABSTRACT Virus-infected plants often display developmental abnormalities that include stunting, leaf curling, and the loss of apical dominance. In this study, the helicase domain of the Tobacco mosaic virus (TMV) 126- and/or 183-kDa replicase protein(s) was found to interact with the Arabidopsis Aux/IAA protein PAP1 (also named IAA26), a putative regulator of auxin response genes involved in plant development. To investigate the role of this interaction in the display of symptoms, a TMV mutant defective in the PAP1 interaction was identified. This mutant replicated and moved normally in Arabidopsis but induced attenuated developmental symptoms. Additionally, transgenic plants in which the accumulation of PAP1 mRNA was silenced exhibit symptoms like those of virus-infected plants. In uninfected tissues, ectopically expressed PAP1 accumulated and localized to the nucleus. However, in TMV-infected tissues, PAP1 failed to accumulate to significant levels and did not localize to the nucleus, suggesting that interaction with the TMV replicase protein disrupts PAP1 localization. The consequences of this interaction would affect PAP1's putative function as a transcriptional regulator of auxin response genes. This is supported by gene expression data indicating that ∼30% of the Arabidopsis genes displaying transcriptional alterations in response to TMV contain multiple auxin response promoter elements. Combined, these data indicate that the TMV replicase protein interferes with the plant's auxin response system to induce specific disease symptoms.

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