scholarly journals The tumor suppressor BRCA1-BARD1 complex localizes to the synaptonemal complex and regulates recombination under meiotic dysfunction in Caenorhabditis elegans

PLoS Genetics ◽  
2018 ◽  
Vol 14 (11) ◽  
pp. e1007701 ◽  
Author(s):  
Qianyan Li ◽  
Takamune T. Saito ◽  
Marina Martinez-Garcia ◽  
Alison J. Deshong ◽  
Saravanapriah Nadarajan ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Tumor Suppressor ◽  
Synaptonemal Complex

scholarly journals The tumor suppressor BRCA1/BARD1 complex localizes to the synaptonemal complex and regulates recombination under meiotic dysfunction in Caenorhabditis elegans

2018 ◽  
Author(s):  
Qianyan Li ◽  
Takamune T. Saito ◽  
Alison J. Deshong ◽  
Marina Martinez Garcia ◽  
Saravanapriah Nadarajan ◽  
...  
Keyword(s):  
Dna Damage ◽  
Caenorhabditis Elegans ◽  
Tumor Suppressor ◽  
Homologous Recombination ◽  
Synaptonemal Complex ◽  
Meiotic Recombination ◽  
Dna Damage Repair ◽  
Chromosome Synapsis ◽  
Brca1 Mutations ◽  
Damage Repair

AbstractBreast cancer susceptibility gene 1(BRCA1) and binding partner BRCA1-associated RING domain protein 1 (BARD1) form an essential E3 ubiquitin ligase important for DNA damage repair and homologous recombination. In Caenorhabditis elegans BRCA1/BRC-1 and BARD1/BRD-1 orthologs are not essential, but function in DNA damage repair and homologous recombination, as well as in meiosis. In proliferating germ cells and in early meiotic prophase, BRC-1 and BRD-1 are nucleoplasmic, with enrichment at foci that partially overlap with the recombinase RAD-51. In mid-pachytene, BRC-1 and BRD-1 are observed on tracks, before concentrating to the short arms of bivalents, co-localizing with a central region component of the synaptonemal complex. We found that BRD-1 is essential for BRC-1 to associate with chromatin and the synaptonemal complex, but BRC-1 is not required for BRD-1 localization; the complex fails to properly localize in the absence of either meiotic recombination or chromosome synapsis. Inactivation of BRC-1/BRD-1 enhances the embryonic lethality of mutants that perturb chromosome synapsis and crossover recombination, suggesting that BRC-1/BRD-1 plays an important role in monitoring recombination in the context of the synaptonemal complex. We discovered that BRC-1/BRD-1 stabilizes the RAD51 filament when the formation of a crossover-intermediate is disrupted. Further, in the absence of BRC-1/BRD-1 crossover distribution is altered, and under meiotic dysfunction, crossover numbers are perturbed. Together, our studies indicate that BRC-1/BRD-1 localizes to the synaptonemal complex where it serves a checkpoint function to monitor and modulate meiotic recombination.Project SummaryOur genomes are passed down from one generation to the next through the specialized cell division program of meiosis. Meiosis is highly regulated to coordinate both the large scale chromosomal and fine scale DNA events to ensure fidelity. We analyzed the role of the tumor suppressor BRCA1/BARD1 complex in meiosis in the worm, Caenorhabditis elegans. We find that BRCA1/BARD1 localizes dynamically to the proteinaeous structure that aligns maternal and paternal chromosomes, where it regulates crossover recombination. Although BRCA1/BARD1 mutants have only subtle meiotic defects, we show that this complex plays a critical role in meiotic recombination when meiosis is perturbed. These results highlight the complexity of ensuring accurate transmission of the genome and uncover the requirement for this conserved complex in meiosis. As women carrying BRCA1 mutations with no indication of cancer have fertility defects, our results provide insight into why BRCA1 mutations impact reproductive success.

scholarly journals The CSN/COP9 Signalosome Regulates Synaptonemal Complex Assembly during Meiotic Prophase I of Caenorhabditis elegans

PLoS Genetics ◽  
2014 ◽  
Vol 10 (11) ◽  
pp. e1004757 ◽  
Author(s):  
Heather Brockway ◽  
Nathan Balukoff ◽  
Martha Dean ◽  
Benjamin Alleva ◽  
Sarit Smolikove
Keyword(s):  
Caenorhabditis Elegans ◽  
Synaptonemal Complex ◽  
Meiotic Prophase ◽  
Cop9 Signalosome ◽  
Complex Assembly ◽  
Prophase I ◽  
Meiotic Prophase I

scholarly journals BRCA1-BARD1 associate with the synaptonemal complex and pro-crossover factors and influence RAD-51 dynamics during Caenorhabditis elegans meiosis

PLoS Genetics ◽  
2018 ◽  
Vol 14 (11) ◽  
pp. e1007653 ◽  
Author(s):  
Eva Janisiw ◽  
Maria Rosaria Dello Stritto ◽  
Verena Jantsch ◽  
Nicola Silva
Keyword(s):  
Caenorhabditis Elegans ◽  
Synaptonemal Complex

scholarly journals CRL4 regulates recombination and synaptonemal complex aggregation in the Caenorhabditis elegans germline

PLoS Genetics ◽  
2019 ◽  
Vol 15 (11) ◽  
pp. e1008486 ◽  
Author(s):  
Benjamin Alleva ◽  
Sean Clausen ◽  
Emily Koury ◽  
Adam Hefel ◽  
Sarit Smolikove
Keyword(s):  
Caenorhabditis Elegans ◽  
Synaptonemal Complex

scholarly journals Crossing over is coupled to late meiotic prophase bivalent differentiation through asymmetric disassembly of the SC

2005 ◽  
Vol 168 (5) ◽  
pp. 683-689 ◽  
Author(s):  
Kentaro Nabeshima ◽  
Anne M. Villeneuve ◽  
Monica P. Colaiácovo
Keyword(s):  
Caenorhabditis Elegans ◽  
Symmetry Breaking ◽  
Synaptonemal Complex ◽  
Central Region ◽  
Meiotic Prophase ◽  
Homologous Chromosome ◽  
Meiotic Chromosome ◽  
Crossing Over ◽  
Γ Irradiation ◽  
Irradiation Treatment

Homologous chromosome pairs (bivalents) undergo restructuring during meiotic prophase to convert a configuration that promotes crossover recombination into one that promotes bipolar spindle attachment and localized cohesion loss. We have imaged remodeling of meiotic chromosome structures after pachytene exit in Caenorhabditis elegans. Chromosome shortening during diplonema is accompanied by coiling of chromosome axes and highly asymmetric departure of synaptonemal complex (SC) central region proteins SYP-1 and SYP-2, which diminish over most of the length of each desynapsing bivalent while becoming concentrated on axis segments distal to the single emerging chiasma. This and other manifestations of asymmetry along chromosomes are lost in synapsis-proficient crossover-defective mutants, which often retain SYP-1,2 along the full lengths of coiled diplotene axes. Moreover, a γ-irradiation treatment that restores crossovers in the spo-11 mutant also restores asymmetry of SYP-1 localization. We propose that crossovers or crossover precursors serve as symmetry-breaking events that promote differentiation of subregions of the bivalent by triggering asymmetric disassembly of the SC.

scholarly journals A compartmentalized signaling network mediates crossover control in meiosis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Liangyu Zhang ◽  
Simone Köhler ◽  
Regina Rillo-Bohn ◽  
Abby F Dernburg
Keyword(s):  
Caenorhabditis Elegans ◽  
Symmetry Breaking ◽  
Synaptonemal Complex ◽  
Chromosome Segregation ◽  
Molecular Basis ◽  
Liquid Crystalline ◽  
Ring Finger ◽  
Homologous Chromosomes ◽  
Crossover Interference ◽  
Ring Finger Proteins

During meiosis, each pair of homologous chromosomes typically undergoes at least one crossover (crossover assurance), but these exchanges are strictly limited in number and widely spaced along chromosomes (crossover interference). The molecular basis for this chromosome-wide regulation remains mysterious. A family of meiotic RING finger proteins has been implicated in crossover regulation across eukaryotes. Caenorhabditis elegans expresses four such proteins, of which one (ZHP-3) is known to be required for crossovers. Here we investigate the functions of ZHP-1, ZHP-2, and ZHP-4. We find that all four ZHP proteins, like their homologs in other species, localize to the synaptonemal complex, an unusual, liquid crystalline compartment that assembles between paired homologs. Together they promote accumulation of pro-crossover factors, including ZHP-3 and ZHP-4, at a single recombination intermediate, thereby patterning exchanges along paired chromosomes. These proteins also act at the top of a hierarchical, symmetry-breaking process that enables crossovers to direct accurate chromosome segregation.

scholarly journals First person – Éva Saskői

2020 ◽  
Vol 13 (10) ◽  
pp. dmm047407
Keyword(s):  
Caenorhabditis Elegans ◽  
Tumor Suppressor ◽  
Early Career ◽  
Disease Models ◽  
First Person ◽  
Early Career Researchers ◽  
Selection Of

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Éva Saskői is first author on ‘The SDHB Arg230His mutation causing familial paraganglioma alters glycolysis in a new Caenorhabditis elegans model’, published in DMM. Éva is a PhD student in the lab of Krisztina Takács-Vellai at Eötvös Lorand University, Budapest, Hungary, investigating the developmental functions of tumor suppressor homologs in Caenorhabditis elegans.

scholarly journals Regulation of Hypoxia-Inducible mRNAs by the von Hippel-Lindau Tumor Suppressor Protein Requires Binding to Complexes Containing Elongins B/C and Cul2

1998 ◽  
Vol 18 (2) ◽  
pp. 732-741 ◽  
Author(s):  
Kim M. Lonergan ◽  
Othon Iliopoulos ◽  
Michael Ohh ◽  
Takumi Kamura ◽  
Ronald C. Conaway ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Tumor Suppressor ◽  
Tumor Suppressor Protein ◽  
Human Homolog ◽  
Von Hippel Lindau ◽  
Specific Proteins ◽  
Apparent Similarity

ABSTRACT The von Hippel-Lindau tumor suppressor protein (pVHL) binds to elongins B and C and posttranscriptionally regulates the accumulation of hypoxia-inducible mRNAs under normoxic (21% O2) conditions. Here we report that pVHL binds, via elongin C, to the human homolog of the Caenorhabditis elegans Cul2 protein. Coimmunoprecipitation and chromatographic copurification data suggest that pVHL-Cul2 complexes exist in native cells. pVHL mutants that were unable to bind to complexes containing elongin C and Cul2 were likewise unable to inhibit the accumulation of hypoxia-inducible mRNAs. A model for the regulation of hypoxia-inducible mRNAs by pVHL is presented based on the apparent similarity of elongin C and Cul2 to Skp1 and Cdc53, respectively. These latter proteins form complexes that target specific proteins for ubiquitin-dependent proteolysis.

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