scholarly journals SCFCdc4 ubiquitin ligase regulates synaptonemal complex formation during meiosis

2020 ◽  
Author(s):  
Zhihui Zhu ◽  
Mohammad Bani Ismail ◽  
Miki Shinohara ◽  
Akira Shinohara

AbstractHomologous chromosomes pair with each other during meiosis, culminating in the formation of the synaptonemal complex (SC), which is coupled with meiotic recombination. In this study, we showed that a meiosis-specific depletion mutant of a cullin (Cdc53) of the SCF (Skp-Cullin-F-box) ubiquitin ligase, which plays a critical role in cell cycle regulation during mitosis, is deficient in SC formation, but is proficient in the formation of crossovers, indicating uncoupling of meiotic recombination with SC formation in the mutant. Furthermore, the deletion of the PCH2 gene encoding a meiosis-specific AAA+ ATPase suppresses SC-assembly defect induced by CDC53 depletion. On the other hand, the pch2 cdc53 double mutant is defective in meiotic crossover formation, suggesting the SC assembly with unrepaired DSBs. A temperature-sensitive mutant of the CDC4, which encodes a F-box protein of the SCF, shows similar meiotic defects to the CDC53 depletion mutant. These suggest that SCFCdc4, probably SCFCdc4-dependnet protein ubiquitylation, regulates and collaborates with Pch2 in SC assembly and meiotic recombination.SummaryDuring meiosis, homologous chromosomes pair with each other and form the synaptonemal complex (SC). In this study, components of the SCF (Skp-Cullin-F-box) ubiquitin ligase, Cdc53 and Cdc4, are required for SC formation. A meiosis-specific AAA+ ATPase Pch2 antagonize the functions of Cdc53 and Cdc4 for proper SC assembly.

2020 ◽  
Vol 4 (2) ◽  
pp. e202000933
Author(s):  
Zhihui Zhu ◽  
Mohammad Bani Ismail ◽  
Miki Shinohara ◽  
Akira Shinohara

Homologous chromosomes pair with each other during meiosis, culminating in the formation of the synaptonemal complex (SC), which is coupled with meiotic recombination. In this study, we showed that a meiosis-specific depletion mutant of a cullin (Cdc53) in the SCF (Skp-Cullin-F-box) ubiquitin ligase, which plays a critical role in cell cycle regulation during mitosis, is deficient in SC formation. However, the mutant is proficient in forming crossovers, indicating the uncoupling of meiotic recombination with SC formation in the mutant. Furthermore, the deletion of the PCH2 gene encoding a meiosis-specific AAA+ ATPase suppresses SC-assembly defects induced by CDC53 depletion. On the other hand, the pch2 cdc53 double mutant is defective in meiotic crossover formation, suggesting the assembly of SC with unrepaired DNA double-strand breaks. A temperature-sensitive mutant of CDC4, which encodes an F-box protein of SCF, shows meiotic defects similar to those of the CDC53-depletion mutant. These results suggest that SCFCdc4, probably SCFCdc4-dependent protein ubiquitylation, regulates and collaborates with Pch2 in SC assembly and meiotic recombination.


2021 ◽  
Author(s):  
Liangyu Zhang ◽  
Weston Stauffer ◽  
David Zwicker ◽  
Abby F. Dernburg

AbstractMeiotic recombination is highly regulated to ensure precise segregation of homologous chromosomes. Evidence from diverse organisms indicates that the synaptonemal complex (SC), which assembles between paired chromosomes, plays essential roles in crossover formation and patterning. Several additional “pro-crossover” proteins are also required for recombination intermediates to become crossovers. These typically form multiple foci or recombination nodules along SCs, and later accumulate at fewer, widely spaced sites. Here we report that in C. elegans CDK-2 is required to stabilize all crossover intermediates and stabilizes interactions among pro-crossover factors by phosphorylating MSH-5. Additionally, we show that the conserved RING domain proteins ZHP-3/4 diffuse along the SC and remain dynamic following their accumulation at recombination sites. Based on these and previous findings we propose a model in which recombination nodules arise through spatially restricted biomolecular condensation and then undergo a regulated coarsening process, resulting in crossover interference.


1997 ◽  
Vol 139 (2) ◽  
pp. 459-467 ◽  
Author(s):  
Carol A. Bascom-Slack ◽  
Dean S. Dawson

The recognition and alignment of homologous chromosomes early in meiosis is essential for their subsequent segregation at anaphase I; however, the mechanism by which this occurs is unknown. We demonstrate here that, in the absence of the molecular motor, Kar3p, meiotic cells are blocked with prophase monopolar microtubule arrays and incomplete synaptonemal complex (SC) formation. kar3 mutants exhibit very low levels of heteroallelic recombination. kar3 mutants do produce double-strand breaks that act as initiation sites for meiotic recombination in yeast, but at levels severalfold reduced from wild-type. These data are consistent with a meiotic role for Kar3p in the events that culminate in synapsis of homologues.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ofer Rog ◽  
Simone Köhler ◽  
Abby F Dernburg

The synaptonemal complex (SC) is a polymer that spans ~100 nm between paired homologous chromosomes during meiosis. Its striated, periodic appearance in electron micrographs led to the idea that transverse filaments within this structure ‘crosslink’ the axes of homologous chromosomes, stabilizing their pairing. SC proteins can also form polycomplexes, three-dimensional lattices that recapitulate the periodic structure of SCs but do not associate with chromosomes. Here we provide evidence that SCs and polycomplexes contain mobile subunits and that their assembly is promoted by weak hydrophobic interactions, indicative of a liquid crystalline phase. We further show that in the absence of recombination intermediates, polycomplexes recapitulate the dynamic localization of pro-crossover factors during meiotic progression, revealing how the SC might act as a conduit to regulate chromosome-wide crossover distribution. Properties unique to liquid crystals likely enable long-range signal transduction along meiotic chromosomes and underlie the rapid evolution of SC proteins.


2002 ◽  
Vol 13 (1) ◽  
pp. 211-224 ◽  
Author(s):  
Satoshi Katayama ◽  
Kenji Kitamura ◽  
Anna Lehmann ◽  
Osamu Nikaido ◽  
Takashi Toda

The Skp1-Cullin-1/Cdc53-F-box protein (SCF) ubiquitin ligase plays an important role in various biological processes. In this enzyme complex, a variety of F-box proteins act as receptors that recruit substrates. We have identified a fission yeast gene encoding a novel F-box protein Pof3, which contains, in addition to the F-box, a tetratricopeptide repeat motif in its N terminus and a leucine-rich-repeat motif in the C terminus, two ubiquitous protein–protein interaction domains. Pof3 forms a complex with Skp1 and Pcu1 (fission yeast cullin-1), suggesting that Pof3 functions as an adaptor for specific substrates. In the absence of Pof3, cells exhibit a number of phenotypes reminiscent of genome integrity defects. These include G2 cell cycle delay, hypersensitivity to UV, appearance of lagging chromosomes, and a high rate of chromosome loss.pof3 deletion strains are viable because the DNA damage checkpoint is continuously activated in the mutant, and this leads to G2 cell cycle delay, thereby preventing the mutant from committing lethal mitosis. Pof3 localizes to the nucleus during the cell cycle. Molecular analysis reveals that in this mutant the telomere is substantially shortened and furthermore transcriptional silencing at the telomere is alleviated. The results highlight a role of the SCFPof3 ubiquitin ligase in genome integrity via maintaining chromatin structures.


2021 ◽  
Author(s):  
Richard Cardoso da Silva ◽  
Gerben Vader

AbstractThe generally conserved AAA+ ATPase Pch2/TRIP13 is involved in diverse aspects of meiosis, such as prophase checkpoint function, DNA break regulation, and meiotic recombination. The controlled recruitment of Pch2 to meiotic chromosomes allows it to use its ATPase activity to influence HORMA protein-dependent signaling. Because of the connection between Pch2 chromosomal recruitment and its functional roles in meiosis, it is important to reveal the molecular details that govern Pch2 localization. Here, we review the current understanding of the different factors that control the recruitment of Pch2 to meiotic chromosomes, with a focus on research performed in budding yeast. During meiosis in this organism, Pch2 is enriched within the nucleolus, where it likely associates with the specialized chromatin of the ribosomal (r)DNA. Pch2 is also found on non-rDNA euchromatin, where its recruitment is contingent on Zip1, a component of the synaptonemal complex (SC) that assembles between homologous chromosomes. We discuss recent findings connecting the recruitment of Pch2 with its association with the Origin Recognition Complex (ORC) and reliance on RNA Polymerase II-dependent transcription. In total, we provide a comprehensive overview of the pathways that control the chromosomal association of an important meiotic regulator.


2020 ◽  
Vol 220 (2) ◽  
Author(s):  
Pedro Barbosa ◽  
Liudmila Zhaunova ◽  
Simona Debilio ◽  
Verdiana Steccanella ◽  
Van Kelly ◽  
...  

Meiosis creates genetic diversity by recombination and segregation of chromosomes. The synaptonemal complex assembles during meiotic prophase I and assists faithful exchanges between homologous chromosomes, but how its assembly/disassembly is regulated remains to be understood. Here, we report how two major posttranslational modifications, phosphorylation and ubiquitination, cooperate to promote synaptonemal complex assembly. We found that the ubiquitin ligase complex SCF is important for assembly and maintenance of the synaptonemal complex in Drosophila female meiosis. This function of SCF is mediated by two substrate-recognizing F-box proteins, Slmb/βTrcp and Fbxo42. SCF-Fbxo42 down-regulates the phosphatase subunit PP2A-B56, which is important for synaptonemal complex assembly and maintenance.


Development ◽  
2001 ◽  
Vol 128 (14) ◽  
pp. 2735-2746
Author(s):  
Dazhong Zhao ◽  
Qilu Yu ◽  
Min Chen ◽  
Hong Ma

The Arabidopsis floral regulatory genes APETALA3 (AP3) and PISTILLATA (PI) are required for the B function according to the ABC model for floral organ identity. AP3 and PI expression are positively regulated by the LEAFY (LFY) and UNUSUAL FLORAL ORGANS (UFO) genes. UFO encodes an F-box protein, and we have shown previously that UFO genetically interacts with the ASK1 gene encoding a SKP1 homologue; both the F-box containing protein and SKP1 are subunits of ubiquitin ligases. We show here that the ask1-1 mutation can enhance the floral phenotypes of weak lfy and ap3 mutants; therefore, like UFO, ASK1 also interacts with LFY and AP3 genetically. Furthermore, our results from RNA in situ hybridizations indicate that ASK1 regulates early AP3 and PI expression. These results support the idea that UFO and ASK1 together positively regulate AP3 and PI expression. We propose that the UFO and ASK1 proteins are components of a ubiquitin ligase that mediates the proteolysis of a repressor of AP3 and PI expression. Our genetic studies also indicate that ASK1 and UFO play a role in regulating the number of floral organ primordia, and we discuss possible mechanisms for such a regulation.


2002 ◽  
Vol 13 (6) ◽  
pp. 1916-1928 ◽  
Author(s):  
Wen-Hui Shen ◽  
Yves Parmentier ◽  
Hanjo Hellmann ◽  
Esther Lechner ◽  
Aiwu Dong ◽  
...  

The SCF (for SKP1, Cullin/CDC53,F-box protein) ubiquitin ligase targets a number of cell cycle regulators, transcription factors, and other proteins for degradation in yeast and mammalian cells. Recent genetic studies demonstrate that plant F-box proteins are involved in auxin responses, jasmonate signaling, flower morphogenesis, photocontrol of circadian clocks, and leaf senescence, implying a large spectrum of functions for the SCF pathway in plant development. Here, we present a molecular and functional characterization of plant cullins. TheArabidopsis genome contains 11 cullin-related genes. Complementation assays revealed that AtCUL1 but not AtCUL4 can functionally complement the yeast cdc53 mutant.Arabidopsis mutants containing transfer DNA (T-DNA) insertions in the AtCUL1 gene were shown to display an arrest in early embryogenesis. Consistently, both the transcript and the protein of the AtCUL1 gene were found to accumulate in embryos. The AtCUL1 protein localized mainly in the nucleus but also weakly in the cytoplasm during interphase and colocalized with the mitotic spindle in metaphase. Our results demonstrate a critical role for the SCF ubiquitin ligase inArabidopsis embryogenesis.


Genetics ◽  
1992 ◽  
Vol 130 (1) ◽  
pp. 59-69
Author(s):  
J Bhargava ◽  
J Engebrecht ◽  
G S Roeder

Abstract A mutation at the REC102 locus was identified in a screen for yeast mutants that produce inviable spores. rec102 spore lethality is rescued by a spo13 mutation, which causes cells to bypass the meiosis I division. The rec102 mutation completely eliminates meiotically induced gene conversion and crossing over but has no effect on mitotic recombination frequencies. Cytological studies indicate that the rec102 mutant makes axial elements (precursors to the synaptonemal complex), but homologous chromosomes fail to synapse. In addition, meiotic chromosome segregation is significantly delayed in rec102 strains. Studies of double and triple mutants indicate that the REC102 protein acts before the RAD52 gene product in the meiotic recombination pathway. The REC102 gene was cloned based on complementation of the mutant defect and the gene was mapped to chromosome XII between CDC25 and STE11.


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