scholarly journals Spermatoproteasome-deficient mice are proficient in meiotic DNA repair but defective in meiotic exit

2018 ◽  
Author(s):  
Laura Gómez-H ◽  
Natalia Felipe-Medina ◽  
Yazmine B. Condezo ◽  
Rodrigo Garcia-Valiente ◽  
Isabel Ramos ◽  
...  
Keyword(s):  
Dna Repair ◽  
Genetic Analysis ◽  
Synaptonemal Complex ◽  
Meiotic Recombination ◽  
Ubiquitin Proteasome System ◽  
Crossing Over ◽  
Structural Framework ◽  
Early Spermatid ◽  
Ubiquitin Proteasome ◽  
Deficient Mice

AbstractMeiotic recombination generates crossovers which are essential to ensure genome haploidization. The ubiquitin proteasome system regulates meiotic recombination through its association to the synaptonemal complex, a ‘zipper’-like structure that holds homologs and provides the structural framework for meiotic recombination. Here we show that the testis-specific α4s subunit (PSMA8) of the spermatoproteasome is located at the synaptonemal complex and is essential for the assembly of its activator PA200. Accordingly, synapsis-deficient mice show delocalization of PSMA8 from the synaptonemal complex. Genetic analysis of Psma8-deficient mice shows normal meiotic DNA repair, crossing over formation and an increase of spermatocytes at metaphase I and metaphase II which either enter into apoptosis or slip to give rise to an early spermatid arrest and infertility. Thus, spermatoproteasome-dependent histone degradation is dispensable for meiotic recombination. We show that PSMA8 deficiency alters the proteostasis of several key meiotic players such as acetylated histones, SYCP3, SYCP1, CDK1 and TRIP13 which in turn leads to an aberrant meiotic exit and early spermatid arrest prior to the histone displacement process that take place subsequently.

scholarly journals The ubiquitin-proteasome system in cancer, a major player in DNA repair. Part 2: transcriptional regulation

2009 ◽  
Vol 13 (9b) ◽  
pp. 3019-3031 ◽  
Author(s):  
Panagiotis J. Vlachostergios ◽  
Anna Patrikidou ◽  
Danai D. Daliani ◽  
Christos N. Papandreou
Keyword(s):  
Dna Repair ◽  
Transcriptional Regulation ◽  
Ubiquitin Proteasome System ◽  
Major Player ◽  
Ubiquitin Proteasome

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.

scholarly journals A SUMO-ubiquitin relay recruits proteasomes to chromosome axes to regulate meiotic recombination

Science ◽  
2017 ◽  
Vol 355 (6323) ◽  
pp. 403-407 ◽  
Author(s):  
H. B. D. Prasada Rao ◽  
Huanyu Qiao ◽  
Shubhang K. Bhatt ◽  
Logan R. J. Bailey ◽  
Hung D. Tran ◽  
...  
Keyword(s):  
Meiotic Recombination ◽  
Meiotic Prophase ◽  
Meiotic Chromosome ◽  
Ubiquitin Proteasome System ◽  
Protein Stabilization ◽  
E3 Ligases ◽  
Sumo Conjugation ◽  
Ubiquitin Proteasome

Meiosis produces haploid gametes through a succession of chromosomal events, including pairing, synapsis, and recombination. Mechanisms that orchestrate these events remain poorly understood. We found that the SUMO (small ubiquitin-like modifier)–modification and ubiquitin-proteasome systems regulate the major events of meiotic prophase in mouse. Interdependent localization of SUMO, ubiquitin, and proteasomes along chromosome axes was mediated largely by RNF212 and HEI10, two E3 ligases that are also essential for crossover recombination. RNF212-dependent SUMO conjugation effected a checkpointlike process that stalls recombination by rendering the turnover of a subset of recombination factors dependent on HEI10-mediated ubiquitylation. We propose that SUMO conjugation establishes a precondition for designating crossover sites via selective protein stabilization. Thus, meiotic chromosome axes are hubs for regulated proteolysis via SUMO-dependent control of the ubiquitin-proteasome system.

scholarly journals Role of the ubiquitin–proteasome system in cardiac dysfunction of adipose triglyceride lipase-deficient mice

2014 ◽  
Vol 77 ◽  
pp. 11-19 ◽  
Author(s):  
Marion Mussbacher ◽  
Heike Stessel ◽  
Gerald Wölkart ◽  
Guenter Haemmerle ◽  
Rudolf Zechner ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Ubiquitin Proteasome System ◽  
Adipose Triglyceride Lipase ◽  
Triglyceride Lipase ◽  
Ubiquitin Proteasome ◽  
Deficient Mice

scholarly journals Two Genes Required for Meiotic Recombination in Drosophila Are Expressed From a Dicistronic Message

Genetics ◽  
2000 ◽  
Vol 154 (4) ◽  
pp. 1735-1746
Author(s):  
H Liu ◽  
J K Jang ◽  
J Graham ◽  
K Nycz ◽  
K S McKim
Keyword(s):  
Genetic Analysis ◽  
Normal Level ◽  
Meiotic Recombination ◽  
Double Mutant ◽  
Transcription Unit ◽  
Holliday Junction ◽  
Crossing Over ◽  
Mutant Analysis ◽  
Recombination Pathway ◽  
Recombination Gene

Abstract We have isolated two alleles of a previously unidentified meiotic recombination gene, mei-217. Genetic analysis of these mutants shows that mei-217 is a typical “precondition” gene. The phenotypes of the mutants are meiosis specific. The strongest allele has <10% of the normal level of crossing over, and the residual events are distributed abnormally. We have used double mutant analysis to position mei-217 in the meiotic recombination pathway. In general, mutations causing defects in the initiation of meiotic recombination are epistatic to mutations in mei-41 and spnB. These two mutations, however, are epistatic to mei-217, suggesting that recombination is initiated normally in mei-217 mutants. It is likely that mei-217 mutants are able to make Holliday junction intermediates but are defective in the production of crossovers. These phenotypes are most similar to mutants of the mei-218 gene. This is striking because mei-217 and mei-218 are part of the same transcription unit and are most likely produced from a dicistronic message.

Fas expression promotes proteasomal activity in toxin-induced parkinsonism

2012 ◽  
Vol 24 (3) ◽  
pp. 166-171
Author(s):  
Anne M. Landau ◽  
Rosmarie Siegrist-Johnstone ◽  
Julie Desbarats
Keyword(s):  
Neuroblastoma Cells ◽  
Death Receptor ◽  
Protein Aggregates ◽  
Ubiquitin Proteasome System ◽  
Wild Type ◽  
Proteasomal Activity ◽  
Ubiquitin Proteasome ◽  
Deficient Mice

Objective: Fas (CD95), commonly categorised as a death receptor due to its well-defined role in apoptosis, can paradoxically also promote neuroprotection. We have previously found that defects in Fas signalling render mice highly susceptible to neural degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease (PD). Decreased activity of the ubiquitin proteasome system and accumulation of protein aggregates are implicated in PD pathogenesis. Here, we investigate the relationship between Fas and ubiquitin proteasomal activity in neuronal cells.Methods: We performed proteasome assays in neuroblastoma cells and in midbrain cultures of wild-type and Fas-deficient mice.Results: Neuroblastoma cells upregulated proteasomal activity in response to an activating Fas antibody in vitro. Furthermore, neural tissue from Fas-deficient mice showed decreased proteasomal activity compared with the tissue from wild-type mice when exposed to a PD-inducing toxin in vivo.Conclusion: These findings suggest that mechanisms for Fas-mediated neuroprotection may include Fas-induced upregulation of proteasomal activity, and consequently less accumulation of toxic protein aggregates.

scholarly journals The Ubiquitin-Proteasome System and DNA Repair

10.5772/24431 ◽  
2011 ◽  
Author(s):  
Christine A. ◽  
Emily C. ◽  
Sumita Raha ◽  
Tatjana Paunesku ◽  
Gayle E.
Keyword(s):  
Dna Repair ◽  
Ubiquitin Proteasome System ◽  
Ubiquitin Proteasome

scholarly journals Loss of HR6B Ubiquitin-Conjugating Activity Results in Damaged Synaptonemal Complex Structure and Increased Crossing-Over Frequency during the Male Meiotic Prophase

2003 ◽  
Vol 23 (4) ◽  
pp. 1151-1162 ◽  
Author(s):  
Willy M. Baarends ◽  
Evelyne Wassenaar ◽  
Jos W. Hoogerbrugge ◽  
Gert van Cappellen ◽  
Henk P. Roest ◽  
...  
Keyword(s):  
Dna Repair ◽  
Synaptonemal Complex ◽  
Meiotic Prophase ◽  
Complex Structure ◽  
Crossing Over ◽  
Primary Role ◽  
Repair Protein ◽  
Dna Repair Protein ◽  
Consistent Increase ◽  
Ubiquitin Conjugating Enzymes

ABSTRACT The ubiquitin-conjugating enzymes HR6A and HR6B are the two mammalian homologs of Saccharomyces cerevisiae RAD6. In yeast, RAD6 plays an important role in postreplication DNA repair and in sporulation. HR6B knockout mice are viable, but spermatogenesis is markedly affected during postmeiotic steps, leading to male infertility. In the present study, increased apoptosis of HR6B knockout primary spermatocytes was detected during the first wave of spermatogenesis, indicating that HR6B performs a primary role during the meiotic prophase. Detailed analysis of HR6B knockout pachytene nuclei showed major changes in the synaptonemal complexes. These complexes were found to be longer. In addition, we often found depletion of synaptonemal complex proteins from near telomeric regions in the HR6B knockout pachytene nuclei. Finally, we detected an increased number of foci containing the mismatch DNA repair protein MLH1 in these nuclei, reflecting a remarkable and consistent increase (20 to 25%) in crossing-over frequency. The present findings reveal a specific requirement for the ubiquitin-conjugating activity of HR6B in relation to dynamic aspects of the synaptonemal complex and meiotic recombination in spermatocytes.

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