Caenorhabditis elegans EVL-14/PDS-5 and SCC-3 Are Essential for Sister Chromatid Cohesion in Meiosis and Mitosis

ABSTRACT Sister chromatid cohesion is fundamental for the faithful transmission of chromosomes during both meiosis and mitosis. Proteins involved in this process are highly conserved from yeasts to humans. In screenings for sterile animals with abnormal vulval morphology, mutations in the Caenorhabditis elegans evl-14 and scc-3 genes were isolated. Defects in cell divisions were observed in germ line as well as in vulval and somatic gonad lineages. Through positional cloning of these genes, we have shown that EVL-14 and SCC-3 are likely the only C. elegans homologs of the yeast sister chromatid cohesion proteins Pds5 and Scc3, respectively. Both evl-14 and scc-3 mutants displayed defects in the meiotic germ line. In evl-14 mutants, synaptonemal complexes (SCs) were detectable but more than the usual six DAPI (4′,6′-diamidino-2-phenylindole)-positive structures were seen at diakinesis, suggesting that EVL-14/PDS-5 is important for the maintenance of sister chromatid cohesion in late prophase. In scc-3 mutant animals, normal SCs were not visible and ∼24 DAPI-positive structures were seen at diakinesis, indicating that SCC-3 is necessary for sister chromatid cohesion. Immunostaining revealed that localization of REC-8, a homolog of the yeast meiotic cohesin subunit Rec8, to the chromosomes depends on the presence of SCC-3 but not that of EVL-14/PDS-5. scc-3 RNA interference (RNAi)-treated embryos were 100% lethal and displayed defects in cell divisions. evl-14 RNAi caused a range of phenotypes. These results indicate that EVL-14/PDS-5 and SCC-3 have functions in both mitosis and meiosis.

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Multiple Subunits of the Caenorhabditis elegans Anaphase-Promoting Complex Are Required for Chromosome Segregation During Meiosis I

Genetics ◽

10.1093/genetics/160.2.805 ◽

2002 ◽

Vol 160 (2) ◽

pp. 805-813 ◽

Cited By ~ 3

Author(s):

Edward S Davis ◽

Lucia Wille ◽

Barry A Chestnut ◽

Penny L Sadler ◽

Diane C Shakes ◽

...

Keyword(s):

Rna Interference ◽

Caenorhabditis Elegans ◽

Chromosome Segregation ◽

Sister Chromatid ◽

Sister Chromatid Cohesion ◽

Anaphase Promoting Complex ◽

Genetic Screens ◽

Chromatid Cohesion ◽

Interference Studies ◽

Meiosis I

Abstract Two genes, originally identified in genetic screens for Caenorhabditis elegans mutants that arrest in metaphase of meiosis I, prove to encode subunits of the anaphase-promoting complex or cyclosome (APC/C). RNA interference studies reveal that these and other APC/C subunits are essential for the segregation of chromosomal homologs during meiosis I. Further, chromosome segregation during meiosis I requires APC/C functions in addition to the release of sister chromatid cohesion.

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Mutational Analysis of the Drosophila Sister-Chromatid Cohesion Protein ORD and Its Role in the Maintenance of Centromeric Cohesion

Genetics ◽

10.1093/genetics/146.4.1319 ◽

1997 ◽

Vol 146 (4) ◽

pp. 1319-1331 ◽

Cited By ~ 1

Author(s):

Sharon E Bickel ◽

Dudley W Wyman ◽

Terry L Orr-Weaver

Keyword(s):

Sister Chromatid ◽

Mutational Analysis ◽

Germ Line ◽

Sister Chromatid Cohesion ◽

Chromosome Loss ◽

Male And Female ◽

Chromatid Cohesion ◽

Random Segregation ◽

Kinetochore Function ◽

Segregation Of Chromosomes

The ord gene is required for proper segregation of all chromosomes in both male and female Drosophila meiosis. Here we describe the isolation of a null ord allele and examine the consequences of ablating ord function. Cytologically, meiotic sister-chromatid cohesion is severely disrupted in flies lacking ORD protein. Moreover, the frequency of missegregation in genetic tests is consistent with random segregation of chromosomes through both meiotic divisions, suggesting that sister cohesion may be completely abolished. However, only a slight decrease in viability is observed for ord null flies, indicating that ORD function is not essential for cohesion during somatic mitosis. In addition, we do not observe perturbation of germ-line mitotic divisions in flies lacking ORD activity. Our analysis of weaker ord alleles suggests that ORD is required for proper centromeric cohesion after arm cohesion is released at the metaphase I/anaphase I transition. Finally, although meiotic cohesion is abolished in the ord null fly, chromosome loss is not appreciable. Therefore, ORD activity appears to promote centromeric cohesion during meiosis II but is not essential for kinetochore function during anaphase.

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TOP-2 is differentially required for the proper maintenance of cohesin on meiotic chromosomes in C. elegans spermatogenesis and oogenesis

10.1101/2021.12.26.474225 ◽

2021 ◽

Author(s):

Aimee Jaramillo-Lambert ◽

Christine Kiely Rourke

Keyword(s):

Sister Chromatid ◽

Topoisomerase Ii ◽

Meiotic Chromosome ◽

Sister Chromatid Cohesion ◽

Chromosome Length ◽

Aurora B ◽

Loss Of Function ◽

Late Prophase ◽

Prophase I ◽

Chromatid Cohesion

During meiotic prophase I, accurate segregation of homologous chromosomes requires the establishment of a chromosomes with a meiosis-specific architecture. Sister chromatid cohesins and the enzyme Topoisomerase II are important components of meiotic chromosome axes, but the relationship of these proteins in the context of meiotic chromosome segregation is poorly defined. Here, we analyzed the role of Topoisomerase II (TOP-2) in the timely release of sister chromatid cohesins during spermatogenesis and oogenesis of Caenorhabditis elegans. We show that there is a different requirement for TOP-2 in meiosis of spermatogenesis and oogenesis. The loss-of-function mutation top-2(it7) results in premature REC-8 removal in spermatogenesis, but not oogenesis. This is due to a failure to maintain the HORMA-domain proteins HTP-1 and HTP-2 (HTP-1/2) on chromosome axes at diakinesis and mislocalization of the downstream components that control sister chromatid cohesion release including Aurora B kinase. In oogenesis, top-2(it7) causes a delay in the localization of Aurora B to oocyte chromosomes but can be rescued through premature activation of the maturation promoting factor via knock-down of the inhibitor kinase WEE-1.3. The delay in Aurora B localization is associated with an increase in the length of diakinesis chromosomes and wee-1.3 RNAi mediated rescue of Auorora B localization in top-2(it7) is associated with a decrease in chromosome length. Our results imply that the sex-specific effects of Topoisomerase II on sister chromatid cohesion release are due to differences in the temporal regulation of meiosis and chromosome structure in late prophase I in spermatogenesis and oogenesis.

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Analysis of Meiotic Sister Chromatid Cohesion in Caenorhabditis elegans

Methods in Molecular Biology - Cohesin and Condensin ◽

10.1007/978-1-4939-6545-8_5 ◽

2016 ◽

pp. 65-95 ◽

Cited By ~ 1

Author(s):

Aaron F. Severson

Keyword(s):

Caenorhabditis Elegans ◽

Sister Chromatid ◽

Sister Chromatid Cohesion ◽

Chromatid Cohesion

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Rec8p, a Meiotic Recombination and Sister Chromatid Cohesion Phosphoprotein of the Rad21p Family Conserved from Fission Yeast to Humans

Molecular and Cellular Biology ◽

10.1128/mcb.19.5.3515 ◽

1999 ◽

Vol 19 (5) ◽

pp. 3515-3528 ◽

Cited By ~ 144

Author(s):

Sandro Parisi ◽

Michael J. McKay ◽

Monika Molnar ◽

M. Anne Thompson ◽

Peter J. van der Spek ◽

...

Keyword(s):

Fission Yeast ◽

Sister Chromatid ◽

Germ Line ◽

Sequence Similarity ◽

Sister Chromatid Cohesion ◽

Specific Expression ◽

Chromatid Cohesion ◽

Prophase Nucleus ◽

Chromosome Iii ◽

Meiosis I

ABSTRACT Our work and that of others defined mitosis-specific (Rad21 subfamily) and meiosis-specific (Rec8 subfamily) proteins involved in sister chromatid cohesion in several eukaryotes, including humans. Mutation of the fission yeast Schizosaccharomyces pombe rec8 gene was previously shown to confer a number of meiotic phenotypes, including strong reduction of recombination frequencies in the central region of chromosome III, absence of linear element polymerization, reduced pairing of homologous chromosomes, reduced sister chromatid cohesion, aberrant chromosome segregation, defects in spore formation, and reduced spore viability. Here we extend the description of recombination reduction to the central regions of chromosomes I and II. We show at the protein level that expression ofrec8 is meiosis specific and that Rec8p localizes to approximately 100 foci per prophase nucleus. Rec8p was present in an unphosphorylated form early in meiotic prophase but was phosphorylated prior to meiosis I, as demonstrated by analysis of the mei4mutant blocked before meiosis I. Evidence for the persistence of Rec8p beyond meiosis I was obtained by analysis of the mutantmes1 blocked before meiosis II. A human gene, which we designate hrec8, showed significant primary sequence similarity to rec8 and was mapped to chromosome 14. High mRNA expression of mouse and human rec8 genes was found only in germ line cells, specifically in testes and, interestingly, in spermatids. hrec8 was also expressed at a low level in the thymus. Sequence similarity and testis-specific expression indicate evolutionarily conserved functions of Rec8p in meiosis. Possible roles of Rec8p in the integration of different meiotic events are discussed.

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hecd-1 Modulates Notch Activity in Caenorhabditis elegans

G3 Genes|Genome|Genetics ◽

10.1534/g3.114.015321 ◽

2015 ◽

Vol 5 (3) ◽

pp. 353-359 ◽

Cited By ~ 3

Author(s):

Yunting Chen ◽

Iva Greenwald

Keyword(s):

Quality Control ◽

Caenorhabditis Elegans ◽

Cell Fate ◽

Germ Line ◽

Notch Pathway ◽

Cell Fate Decisions ◽

Notch Activity ◽

C Elegans ◽

Somatic Gonad ◽

Constitutively Active

Abstract Notch is a receptor that mediates cell–cell interactions that specify binary cell fate decisions in development and tissue homeostasis. Inappropriate Notch signaling is associated with cancer, and mutations in Notch pathway components have been associated with developmental diseases and syndromes. In Caenorhabditis elegans, suppressors of phenotypes associated with constitutively active LIN-12/Notch have identified many conserved core components and direct or indirect modulators. Here, we molecularly identify sel(ar584), originally isolated as a suppressor of a constitutively active allele of lin-12. We show that sel(ar584) is an allele of hecd-1, the ortholog of human HECDT1, a ubiquitin ligase that has been implicated in several different mammalian developmental events. We studied interactions of hecd-1 with lin-12 in the somatic gonad and with the other C. elegans Notch gene, glp-1, in the germ line. We found that hecd-1 acts as a positive modulator of lin-12/Notch activity in a somatic gonad context—the original basis for its isolation—but acts autonomously as a negative modulator of glp-1/Notch activity in the germ line. As the yeast ortholog of HECD-1, Ufd4p, has been shown to function in quality control, and C. elegans HECD-1 has been shown to affect mitochondrial maintenance, we propose that the different genetic interactions between hecd-1 and Notch genes we observed in different cell contexts may reflect differences in quality control regulatory mechanisms or in cellular metabolism.

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Shugoshin is essential for meiotic prophase checkpoints in C. elegans

10.1101/258830 ◽

2018 ◽

Author(s):

Tisha Bohr ◽

Christian R. Nelson ◽

Stefani Giacopazzi ◽

Piero Lamelza ◽

Needhi Bhalla

Keyword(s):

Sister Chromatid ◽

Meiotic Prophase ◽

Meiotic Chromosome ◽

Sister Chromatid Cohesion ◽

Chromosomal Protein ◽

Loss Of Function ◽

Chromosome Architecture ◽

C Elegans ◽

Meiotic Chromosomes ◽

Chromatid Cohesion

AbstractThe conserved factor Shugoshin is dispensable in C. elegans for the two-step loss of sister chromatid cohesion that directs the proper segregation of meiotic chromosomes. We show that the C. elegans ortholog of Shugoshin, SGO-1, is required for checkpoint activity in meiotic prophase. This role in checkpoint function is similar to that of the meiotic chromosomal protein, HTP-3. Null sgo-1 mutants exhibit additional phenotypes similar to that of a partial loss of function allele of HTP-3: premature synaptonemal complex disassembly, the activation of alternate DNA repair pathways and an inability to recruit a conserved effector of the DNA damage pathway, HUS-1. SGO-1 localizes to pre-meiotic nuclei, when HTP-3 is present but not yet loaded onto chromosome axes, suggesting an early role in regulating meiotic chromosome metabolism. We propose that SGO-1 acts during pre-meiotic replication to ensure fully functional meiotic chromosome architecture, rendering these chromosomes competent for checkpoint activity and normal progression of meiotic recombination. Given that most research on Shugoshin has been focused on its regulation of sister chromatid cohesion in meiosis, this novel role may be conserved but previously uncharacterized in other organisms. Further, our findings expand the repertoire of Shugoshin’s functions beyond coordinating regulatory activities at the centromere.

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