Regulation of interference-sensitive crossover distribution ensures crossover assurance in Arabidopsis

2021 ◽  
Vol 118 (47) ◽  
pp. e2107543118
Author(s):  
Xiang Li ◽  
Jun Zhang ◽  
Jiyue Huang ◽  
Jing Xu ◽  
Zhiyu Chen ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Arabidopsis Thaliana ◽  
Mus Musculus ◽  
Distribution Patterns ◽  
Underlying Mechanism ◽  
Class Ii ◽  
Class I ◽  
Wild Type ◽  
Chromosomal Segregation ◽  
Normal Class

During meiosis, crossovers (COs) are typically required to ensure faithful chromosomal segregation. Despite the requirement for at least one CO between each pair of chromosomes, closely spaced double COs are usually underrepresented due to a phenomenon called CO interference. Like Mus musculus and Saccharomyces cerevisiae, Arabidopsis thaliana has both interference-sensitive (Class I) and interference-insensitive (Class II) COs. However, the underlying mechanism controlling CO distribution remains largely elusive. Both AtMUS81 and AtFANCD2 promote the formation of Class II CO. Using both AtHEI10 and AtMLH1 immunostaining, two markers of Class I COs, we show that AtFANCD2 but not AtMUS81 is required for normal Class I CO distribution among chromosomes. Depleting AtFANCD2 leads to a CO distribution pattern that is intermediate between that of wild-type and a Poisson distribution. Moreover, in Atfancm, Atfigl1, and Atrmi1 mutants where increased Class II CO frequency has been reported previously, we observe Class I CO distribution patterns that are strikingly similar to Atfancd2. Surprisingly, we found that AtFANCD2 plays opposite roles in regulating CO frequency in Atfancm compared with either in Atfigl1 or Atrmi1. Together, these results reveal that although AtFANCD2, AtFANCM, AtFIGL1, and AtRMI1 regulate Class II CO frequency by distinct mechanisms, they have similar roles in controlling the distribution of Class I COs among chromosomes.

Mutation at autosomal loci of Chinese hamster ovary cells: involvement of a high-frequency event silencing two linked alleles

1983 ◽  
Vol 3 (7) ◽  
pp. 1172-1181
Author(s):  
W E Bradley
Keyword(s):  
Cell Lines ◽  
Chinese Hamster Ovary ◽  
High Frequency ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Low Frequency ◽  
Class Ii ◽  
Class I ◽  
Wild Type ◽  
Ovary Cells

Two classes of cell lines heterozygous at the galactokinase (glk) locus have been isolated from Chinese hamster ovary cells. Class I, selected by plating nonmutagenized wild-type cells at low density in medium containing 2-deoxygalactose at a partially selective concentration, underwent subsequent mutation to the glk-/- genotype at a low frequency (approximately 10(-6) per cell), which was increased by mutagenesis. Class II heterozygotes, isolated by sib selection from mutagenized wild-type cells, had a higher spontaneous frequency of mutation to the homozygous state (approximately 10(-4) per cell), which was not affected by mutagenesis. About half of the glk-/- mutants derived from a class II heterozygote, but not the heterozygote itself, were functionally hemizygous at the syntenic thymidine kinase (tk) locus. Similarly, a tk+/- heterozygote with characteristics analogous to the class II glk+/- cell lines underwent high-frequency mutation to tk-/-, and most of these mutants, but not the tk+/- heterozygote, were functionally hemizygous at the glk locus. A model is proposed, similar to that for the mutational events at the adenine phosphoribosyl transferase locus (W. E. C. Bradley and D. Letovanec, Somatic Cell Genet. 8:51-66, 1982), of two different events, high and low frequency, being responsible for mutation at either of the linked loci tk and glk. The low-frequency event may be a point mutation, but the high-frequency event, in many instances, involves coordinated inactivation of a portion of a chromosome carrying the two linked alleles. Class II heterozygotes would be generated as a result of a low-frequency event at one allele, and class I heterozygotes would be generated by a high-frequency event. Supporting this model was the demonstration that all class I glk+/- lines examined were functionally hemizygous at tk.

Acute Myeloid Leukemia (AML) with 9q Aberrations Occuring within a Non-Complex Karyotype Is Highly Associated with CEBPA and NPM1 Mutations - A Joint Analysis of the German-Austrian AML Study Group (AMLSG) and Cancer and Leukemia Group B (CALGB).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 762-762
Author(s):  
Andrea Corbacioglu ◽  
Stefan Fröhling ◽  
Peter Paschka ◽  
Guido Marcucci ◽  
Andreas Anhalt ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Class Ii ◽  
Class I ◽  
Joint Analysis ◽  
Complex Karyotype ◽  
Loss Of Function ◽  
Wild Type ◽  
Npm1 Mutation ◽  
Cebpa Mutations ◽  
Group 1

Abstract Background: In a previous study we showed that AML with deletion 9q (9q-) occurring in the context of a non-complex karyotype is associated with CEBPA loss-of-function mutations; their prevalence was 41% (Frohling et al., Genes Chromosomes Cancer2005;42:427). We hypothesized that disruption of CEBPA function and loss of a critical segment of 9q cooperate in leukemogenesis. This is consistent with the model of leukemogenesis, in which mutations from different complementation groups cooperate, e.g., CEBPA mutations, representing the class II mutation impairing differentiation, occur simultaneously with 9q- associated with loss and/or mutation of an as yet unidentified gene that confers the proliferative advantage (class I mutation). 9q- is also associated with t(8;21)/RUNX1/RUNX1T1, another class II mutation. Importantly, in initial studies screening for NPM1 mutations, a few patients (pts) with 9q- were reported to harbor NPM1 mutations. Objective: To evaluate the incidence and clinical significance of mutations in the CEBPA and NPM1 genes in a large series of AML with 9q aberrations. Methods: Fifty-seven pts exhibiting a 9q aberration on chromosomal banding analysis were screened for CEBPA and NPM1 mutations. Pts were classified into three groups: those with 9q- occurring as a sole aberration or together with one additional abnormality other than t(8;21) (n=35); pts with 9q- occurring within a complex karyotype, defined as ≥3 abnormalities (n=10); and pts with 9q- secondary to t(8;21) (n=12). Results: The frequencies of CEBPA and NPM1 mutations in group 1 were 49% and 29%, respectively. Strikingly, either a CEBPA or NPM1 mutation was identified in 27 of the 35 (77%) pts within this subgroup. CEBPA and NPM1 mutations did not occur concurrently. In contrast, only one CEBPA and no NPM1 mutations were detected in group 2; no pt in group 3 had mutations in CEBPA or NPM1. Although the number of pts is still limited, within group 1, pts with CEBPA mutations and those with NPM1 mutations had higher CR rates, 86% and 80%, respectively, than pts with wild-type CEBPA and NPM1, whose CR rate was 57%. Overall survival of 9q- pts with CEBPA mutations was significantly better than that of the remaining pts comprising those with NPM1 mutations and pts with wild-type CEBPA and NPM1 (p=0.03). Conclusions: Abnormalities of 9q occurring in AML pts with a non-complex karyotype and without t(8;21) are highly associated with CEBPA or NPM1 gene mutations. CEBPA and NPM1 mutations are mutually exclusive, a finding that further supports the hypothesis that both CEBPA and NPM1 mutations act as class II mutations, which cooperate with a class I mutation affecting a thus far unknown gene on 9q. Currently, additional pts with 9q- are under investigation.

scholarly journals Three new t-haplotypes of Mus musculus reveal structural similarities to t-haplotypes of Mus domesticus

1988 ◽  
Vol 51 (2) ◽  
pp. 111-119 ◽  
Author(s):  
Jiří Forejt ◽  
Soňa Gregorová ◽  
Petr Jansa
Keyword(s):  
Mus Musculus ◽  
Parental Species ◽  
Class I ◽  
Mus Domesticus ◽  
Male Mice ◽  
Wild Type ◽  
Restriction Fragments ◽  
Alpha Globin

SummaryThree new t-haplotypes, tp 4, tp 12 and tp 14, were isolated from M. musculus male mice captured in Central and East Bohemia, Czechoslovakia, about 400 km from the zone of hybridization between M. musculus and M. domesticus species. Complementation tests have shown that all three new t-haplotypes belong to tw 73 group. When compared with 5 t-haplotypes from M. domesticus they displayed the same pattern of BamHI restriction fragments with H-2 class I genes, and they also shared the t-specific 5·2 kb TaqI fragment of the alpha globin pseudogene. However, they differed from M. domesticus t-haplotypes at the D17Leh443 locus since they all displayed a 10·5 kb MspI fragment, labelled by the Tu443 probe, not found in wild type-chromosomes or in M. domesticus t-haplotypes. A hypothesis is proposed that t-haplotypes in M. domesticus originated by a single successful introgression from a parental species during speciation.

scholarly journals ZYP1 is required for obligate cross-over formation and cross-over interference in Arabidopsis

2021 ◽  
Vol 118 (14) ◽  
pp. e2021671118
Author(s):  
Martin G. France ◽  
Janina Enderle ◽  
Sarah Röhrig ◽  
Holger Puchta ◽  
F. Chris H. Franklin ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Synaptonemal Complex ◽  
Class Ii ◽  
Class I ◽  
Crossing Over ◽  
Wild Type ◽  
Homologous Chromosomes ◽  
Virtual Absence ◽  
Meiotic Progression ◽  
Null Mutants

The synaptonemal complex is a tripartite proteinaceous ultrastructure that forms between homologous chromosomes during prophase I of meiosis in the majority of eukaryotes. It is characterized by the coordinated installation of transverse filament proteins between two lateral elements and is required for wild-type levels of crossing over and meiotic progression. We have generated null mutants of the duplicated Arabidopsis transverse filament genes zyp1a and zyp1b using a combination of T-DNA insertional mutants and targeted CRISPR/Cas mutagenesis. Cytological and genetic analysis of the zyp1 null mutants reveals loss of the obligate chiasma, an increase in recombination map length by 1.3- to 1.7-fold and a virtual absence of cross-over (CO) interference, determined by a significant increase in the number of double COs. At diplotene, the numbers of HEI10 foci, a marker for Class I interference-sensitive COs, are twofold greater in the zyp1 mutant compared to wild type. The increase in recombination in zyp1 does not appear to be due to the Class II interference-insensitive COs as chiasmata were reduced by ∼52% in msh5/zyp1 compared to msh5. These data suggest that ZYP1 limits the formation of closely spaced Class I COs in Arabidopsis. Our data indicate that installation of ZYP1 occurs at ASY1-labeled axial bridges and that loss of the protein disrupts progressive coalignment of the chromosome axes.

Murine T Lymphocytes Incapable of Producing Macrophage Inhibitory Protein-1 Are Impaired in Causing Graft-Versus-Host Disease Across a Class I But Not Class II Major Histocompatibility Complex Barrier

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Jonathan S. Serody ◽  
Donald N. Cook ◽  
Suzanne L. Kirby ◽  
Elizabeth Reap ◽  
Thomas C. Shea ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Graft Versus Host Disease ◽  
Class Ii ◽  
Class I ◽  
Wild Type ◽  
Inhibitory Protein ◽  
Host Disease ◽  
Graft Versus Host

Abstract The routine use of bone marrow transplantation is limited by the occurrence of acute and chronic graft-versus-host disease (GVHD). Current approaches to decreasing the occurrence of GVHD after allogeneic transplantation use T-cell depletion, use immunosuppressive agents, or block costimulatory molecule function. The role of proteins in the recruitment of alloreactive lymphocytes has not been well characterized. Chemokines are a large family of proteins that mediate recruitment of mononuclear cells in vitro and in vivo. To investigate the role of T-cell production of the chemokine macrophage inhibitory protein-1 (MIP-1) in the occurrence of GVHD, splenocytes either from wild-type or from MIP-1−/− mice were administered to class I (B6.C-H2bm1) and class II disparate mice (B6-C-H2bm12). The incidence and severity of GVHD was markedly reduced in bm1 mice receiving splenocytes from MIP-1−/− mice as compared with mice receiving wild-type splenocytes. Bm1 mice receiving MIP-1−/− splenocytes had significantly less weight loss and markedly reduced inflammatory responses in the lung and liver than mice receiving C57BL/6 splenocytes. Bm1 mice receiving MIP-1−/− splenocytes had a markedly decreased production of antichromatin autoantibodies and impaired generation of bm1-specific T lymphocytes versus wild-type mice. However, MIP-1−/− splenocytes easily induced GVHD when administered to bm12 mice. This data show that blockade of chemokine production or function may provide a new approach to the prevention or treatment of GVHD but that chemokines that recruit both CD4+ and CD8+ lymphocytes may need to be targeted.

scholarly journals Molecular strategies for antibody binding and escape of SARS-CoV-2 and its mutations

2021 ◽  
Author(s):  
Mohamed Hendy ◽  
Samuel Kaufman ◽  
Mauricio Ponga
Keyword(s):  
Neutralizing Antibodies ◽  
Class Ii ◽  
Host Cells ◽  
Class I ◽  
Wild Type ◽  
Sharp Decline ◽  
S Protein ◽  
Antibody Class ◽  
Binding Avidity ◽  
Binding Mechanisms

The COVID19 pandemic, caused by SARS-CoV-2, has infected more than 100 million people worldwide. Due to the rapid spreading of SARS-CoV-2 and its impact, it is paramount to find effective treatments against it. Human neutralizing antibodies are an effective method to fight viral infection. However, the recent discovery of new strains that substantially change the S-protein sequence has raised concern about vaccines and antibodies’ effectiveness. Here, we investigated the binding mechanisms between the S-protein and several antibodies. Multiple mutations were included to understand the strategies for antibody escape in new variants. We found that the combination of mutations K417N and E484K produced higher binding energy to ACE2 than the wild type, suggesting higher efficiency to enter host cells. The mutations’ effect depends on the antibody class. While Class I enhances the binding avidity in the presence of N501Y mutation, class II antibodies showed a sharp decline in the binding affinity. Our simulations suggest that Class I antibodies will remain effective against the new strains. In contrast, Class II antibodies will have less affinity to the S-protein, potentially affecting these antibodies’ efficiency.

Murine T Lymphocytes Incapable of Producing Macrophage Inhibitory Protein-1 Are Impaired in Causing Graft-Versus-Host Disease Across a Class I But Not Class II Major Histocompatibility Complex Barrier

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Jonathan S. Serody ◽  
Donald N. Cook ◽  
Suzanne L. Kirby ◽  
Elizabeth Reap ◽  
Thomas C. Shea ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Graft Versus Host Disease ◽  
Class Ii ◽  
Class I ◽  
Wild Type ◽  
Inhibitory Protein ◽  
Host Disease ◽  
Graft Versus Host

The routine use of bone marrow transplantation is limited by the occurrence of acute and chronic graft-versus-host disease (GVHD). Current approaches to decreasing the occurrence of GVHD after allogeneic transplantation use T-cell depletion, use immunosuppressive agents, or block costimulatory molecule function. The role of proteins in the recruitment of alloreactive lymphocytes has not been well characterized. Chemokines are a large family of proteins that mediate recruitment of mononuclear cells in vitro and in vivo. To investigate the role of T-cell production of the chemokine macrophage inhibitory protein-1 (MIP-1) in the occurrence of GVHD, splenocytes either from wild-type or from MIP-1−/− mice were administered to class I (B6.C-H2bm1) and class II disparate mice (B6-C-H2bm12). The incidence and severity of GVHD was markedly reduced in bm1 mice receiving splenocytes from MIP-1−/− mice as compared with mice receiving wild-type splenocytes. Bm1 mice receiving MIP-1−/− splenocytes had significantly less weight loss and markedly reduced inflammatory responses in the lung and liver than mice receiving C57BL/6 splenocytes. Bm1 mice receiving MIP-1−/− splenocytes had a markedly decreased production of antichromatin autoantibodies and impaired generation of bm1-specific T lymphocytes versus wild-type mice. However, MIP-1−/− splenocytes easily induced GVHD when administered to bm12 mice. This data show that blockade of chemokine production or function may provide a new approach to the prevention or treatment of GVHD but that chemokines that recruit both CD4+ and CD8+ lymphocytes may need to be targeted.

scholarly journals Mutation at autosomal loci of Chinese hamster ovary cells: involvement of a high-frequency event silencing two linked alleles.

1983 ◽  
Vol 3 (7) ◽  
pp. 1172-1181 ◽  
Author(s):  
W E Bradley
Keyword(s):  
Cell Lines ◽  
Chinese Hamster Ovary ◽  
High Frequency ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Low Frequency ◽  
Class Ii ◽  
Class I ◽  
Wild Type ◽  
Ovary Cells

Two classes of cell lines heterozygous at the galactokinase (glk) locus have been isolated from Chinese hamster ovary cells. Class I, selected by plating nonmutagenized wild-type cells at low density in medium containing 2-deoxygalactose at a partially selective concentration, underwent subsequent mutation to the glk-/- genotype at a low frequency (approximately 10(-6) per cell), which was increased by mutagenesis. Class II heterozygotes, isolated by sib selection from mutagenized wild-type cells, had a higher spontaneous frequency of mutation to the homozygous state (approximately 10(-4) per cell), which was not affected by mutagenesis. About half of the glk-/- mutants derived from a class II heterozygote, but not the heterozygote itself, were functionally hemizygous at the syntenic thymidine kinase (tk) locus. Similarly, a tk+/- heterozygote with characteristics analogous to the class II glk+/- cell lines underwent high-frequency mutation to tk-/-, and most of these mutants, but not the tk+/- heterozygote, were functionally hemizygous at the glk locus. A model is proposed, similar to that for the mutational events at the adenine phosphoribosyl transferase locus (W. E. C. Bradley and D. Letovanec, Somatic Cell Genet. 8:51-66, 1982), of two different events, high and low frequency, being responsible for mutation at either of the linked loci tk and glk. The low-frequency event may be a point mutation, but the high-frequency event, in many instances, involves coordinated inactivation of a portion of a chromosome carrying the two linked alleles. Class II heterozygotes would be generated as a result of a low-frequency event at one allele, and class I heterozygotes would be generated by a high-frequency event. Supporting this model was the demonstration that all class I glk+/- lines examined were functionally hemizygous at tk.

scholarly journals The Arabidopsis thaliana Class II Formin FH13 Modulates Pollen Tube Growth

2021 ◽  
Vol 12 ◽  
Author(s):  
Eva Kollárová ◽  
Anežka Baquero Forero ◽  
Fatima Cvrčková
Keyword(s):  
Arabidopsis Thaliana ◽  
Pollen Tube ◽  
Pollen Tube Growth ◽  
Tip Growth ◽  
Pollen Tubes ◽  
Class Ii ◽  
Membrane Dynamics ◽  
Tube Growth ◽  
Class I ◽  
Pollen Tube Elongation

Formins are a large, evolutionarily conserved family of actin-nucleating proteins with additional roles in regulating microfilament, microtubule, and membrane dynamics. Angiosperm formins, expressed in both sporophytic and gametophytic tissues, can be divided into two subfamilies, Class I and Class II, each often exhibiting characteristic domain organization. Gametophytically expressed Class I formins have been documented to mediate plasma membrane-based actin assembly in pollen grains and pollen tubes, contributing to proper pollen germination and pollen tube tip growth, and a rice Class II formin, FH5/RMD, has been proposed to act as a positive regulator of pollen tube growth based on mutant phenotype and overexpression data. Here we report functional characterization of the Arabidopsis thaliana pollen-expressed typical Class II formin FH13 (At5g58160). Consistent with published transcriptome data, live-cell imaging in transgenic plants expressing fluorescent protein-tagged FH13 under the control of the FH13 promoter revealed expression in pollen and pollen tubes with non-homogeneous signal distribution in pollen tube cytoplasm, suggesting that this formin functions in the male gametophyte. Surprisingly, fh13 loss of function mutations do not affect plant fertility but result in stimulation of in vitro pollen tube growth, while tagged FH13 overexpression inhibits pollen tube elongation. Pollen tubes of mutants expressing a fluorescent actin marker exhibited possible minor alterations of actin organization. Our results thus indicate that FH13 controls or limits pollen tube growth, or, more generally, that typical Class II formins should be understood as modulators of pollen tube elongation rather than merely components of the molecular apparatus executing tip growth.

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