Correction for Girard et al., Interdependent and separable functions of Caenorhabditis elegans MRN-C complex members couple formation and repair of meiotic DSBs

Faithful inheritance of genetic information through sexual reproduction relies on the formation of crossovers between homologous chromosomes during meiosis, which, in turn, relies on the formation and repair of numerous double-strand breaks (DSBs). As DSBs pose a potential threat to the genome, mechanisms that ensure timely and error-free DSB repair are crucial for successful meiosis. Here, we identify NBS-1, the Caenorhabditis elegans ortholog of the NBS1 (mutated in Nijmegen Breakage Syndrome) subunit of the conserved MRE11-RAD50-NBS1/Xrs2 (MRN) complex, as a key mediator of DSB repair via homologous recombination (HR) during meiosis. Loss of nbs-1 leads to severely reduced loading of recombinase RAD-51, ssDNA binding protein RPA, and pro-crossover factor COSA-1 during meiotic prophase progression; aggregated and fragmented chromosomes at the end of meiotic prophase; and 100% progeny lethality. These phenotypes reflect a role for NBS-1 in processing of meiotic DSBs for HR that is shared with its interacting partners MRE-11-RAD-50 and COM-1 (ortholog of Com1/Sae2/CtIP). Unexpectedly, in contrast to MRE-11 and RAD-50, NBS-1 is not required for meiotic DSB formation. Meiotic defects of the nbs-1 mutant are partially suppressed by abrogation of the nonhomologous end-joining (NHEJ) pathway, indicating a role for NBS-1 in antagonizing NHEJ during meiosis. Our data further reveal that NBS-1 and COM-1 play distinct roles in promoting HR and antagonizing NHEJ. We propose a model in which different components of the MRN-C complex work together to couple meiotic DSB formation with efficient and timely engagement of HR, thereby ensuring crossover formation and restoration of genome integrity before the meiotic divisions.

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The APC/CFZY–1/Cdc20 Complex Coordinates With OMA-1 to Regulate the Oocyte-to-Embryo Transition in Caenorhabditis elegans

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.749654 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yabing Hu ◽

Xuewen Hu ◽

Dongchen Li ◽

Zhenzhen Du ◽

Kun Shi ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Cell Fate ◽

Zinc Finger ◽

Oocyte Maturation ◽

Rna Binding ◽

Gain Of Function ◽

Ccch Zinc Finger ◽

C Complex ◽

Fate Determinants ◽

Cell Fate Determinants

During oocyte maturation and the oocyte-to-embryo transition, key developmental regulators such as RNA-binding proteins coordinate translation of particular messenger RNA (mRNAs) and related developmental processes by binding to their cognate maternal mRNAs. In the nematode Caenorhabditis elegans, these processes are regulated by a set of CCCH zinc finger proteins. Oocyte maturation defective-1 (OMA-1) and OMA-2 are two functionally redundant CCCH zinc finger proteins that turnover rapidly during the first embryonic cell division. These turnovers are required for proper transition from oogenesis to embryogenesis. A gain-of-function mutant of OMA-1, oma-1(zu405), stabilizes and delays degradation of OMA-1, resulting in delayed turnover and mis-segregation of other cell fate determinants, which eventually causes embryonic lethality. We performed a large-scale forward genetic screen to identify suppressors of the oma-1(zu405) mutant. We show here that multiple alleles affecting functions of various anaphase promoting complex/cyclosome (APC/C) subunits, including MAT-1, MAT-2, MAT-3, EMB-30, and FZY-1, suppress the gain-of-function mutant of OMA-1. Transcriptome analysis suggested that overall transcription in early embryos occurred after introducing mutations in APC/C genes into the oma-1(zu405) mutant. Mutations in APC/C genes prevent OMA-1 enrichment in P granules and correct delayed degradation of downstream cell fate determinants including pharynx and intestine in excess-1 (PIE-1), posterior segregation-1 (POS-1), muscle excess-3 (MEX-3), and maternal effect germ-cell defective-1 (MEG-1). We demonstrated that only the activator FZY-1, but not FZR-1, is incorporated in the APC/C complex to regulate the oocyte-to-embryo transition. Our findings suggested a genetic relationship linking the APC/C complex and OMA-1, and support a model in which the APC/C complex promotes P granule accumulation and modifies RNA binding of OMA-1 to regulate the oocyte-to-embryo transition process.

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RPA complexes in Caenorhabditis elegans meiosis; unique roles in replication, meiotic recombination and apoptosis

10.1101/2020.06.27.174912 ◽

2020 ◽

Author(s):

Adam Hefel ◽

Nicholas Cronin ◽

Kailey Harrel ◽

Pooja Patel ◽

Maria Spies ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Homologous Recombination ◽

Meiotic Recombination ◽

Protein A ◽

Replication Protein A ◽

Replication Protein ◽

Filament Formation ◽

C Elegans ◽

Trimeric Complex ◽

Meiotic Dsbs

AbstractReplication Protein A (RPA) is critical complex that acts in replication and promotes homologous recombination by allowing recombinase recruitment to processed DSB ends. Most organisms possess three RPA subunits (RPA1, RPA2, RPA3) that form a trimeric complex critical for viability. The Caenorhabditis elegans genome encodes for RPA-1, RPA-2 and an RPA-2 paralog RPA-4. In our analysis, we determine that RPA-2 is critical for germline replication, and normal repair of meiotic DSBs. Interestingly, RPA-1 but not RPA-2 is essential for replication, contradictory to what is seen in other organisms, that require both subunits. In the germline, both RPA-1/2 and RPA-1/4 complexes form, but RPA-1/4 is less abundant and its formation is repressed by RPA-2. While RPA-4 does not participate in replication or recombination, we find that RPA-4 inhibit RAD-51 filament formation and promotes apoptosis on a subset of damaged nuclei. Altogether these findings point to sub-functionalization and antagonistic roles of RPA complexes in C. elegans.

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Interdependent and separable functions of C. elegans MRN-C complex members couple formation and repair of meiotic DSBs

10.1101/214015 ◽

2017 ◽

Cited By ~ 1

Author(s):

Chloe Girard ◽

Baptiste Roelens ◽

Karl A. Zawadzki ◽

Anne M. Villeneuve

Keyword(s):

Meiotic Prophase ◽

Nijmegen Breakage Syndrome ◽

Dna Lesions ◽

Dna Breaks ◽

Potential Threat ◽

Dsb Repair ◽

Homologous Chromosomes ◽

C Elegans ◽

Meiotic Dsbs ◽

C Complex

AbstractFaithful inheritance of genetic information through sexual reproduction relies on the formation of crossovers between homologous chromosomes during meiosis, which in turn relies on the formation and repair of numerous double-strand DNA breaks (DSBs). As DSBs pose a potential threat to the genome, mechanisms that ensure timely and error-free DSB repair are crucial for successful meiosis. Here we identify NBS-1, the Caenorhabditis elegans ortholog of the NBS1 subunit of the conserved MRE11-RAD50-NBS1/Xrs2 (MRN) complex, as a key mediator of DSB repair via homologous recombination (HR) during meiosis. Loss of nbs-1 leads to: severely reduced loading of recombinase RAD-51, ssDNA binding protein RPA and pro-crossover factor COSA-1 during meiotic prophase progression; aggregated and fragmented chromosomes at the end of meiotic prophase; and 100% progeny lethality. These phenotypes reflect a role for NBS-1 in processing of meiotic DSBs for HR that is shared with its interacting partners MRE-11-RAD-50 and COM-1 (ortholog of Com1/Sae2/CtIP). Unexpectedly, in contrast to MRE-11 and RAD-50, NBS-1 is not required for meiotic DSB formation. Meiotic defects of the nbs-1 mutant are partially suppressed by abrogation of the non-homologous end-joining (NHEJ) pathway, indicating a role for NBS-1 in antagonizing NHEJ during meiosis. Our data further reveal that NBS-1 and COM-1 play distinct roles in promoting HR and antagonizing NHEJ. We propose a model in which different components of the MRN-C complex work together to couple meiotic DSB formation with efficient and timely engagement of HR, thereby ensuring crossover formation and restoration of genome integrity prior to the meiotic divisions.Significance StatementDouble-strand breaks (DSBs) are deleterious DNA lesions, and impairment of the DSB repair machinery can lead to devastating diseases such as the Nijmegen Breakage Syndrome (NBS). During meiosis, DSBs represent a "necessary evil": they are required to promote formation of crossovers between homologous chromosomes. Crossovers in turn ensure correct chromosome inheritance during gamete formation, which is essential for viability and normal development of embryos. During meiosis, numerous DSBs are actively created, so meiotic cells must ensure that all breaks are properly repaired to ensure crossover formation and restore genomic integrity. Here we identify C. elegans NBS-1 as essential to properly process meiotic DSBs, both to promote crossover formation and antagonize an error-prone DSB repair pathway, thereby ensuring faithful chromosome inheritance.

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Review for "The connectome of the Caenorhabditis elegans pharynx"

10.1002/cne.24932/v1/review1 ◽

2020 ◽

Author(s):

Sreekanth Chalasani

Keyword(s):

Caenorhabditis Elegans

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The glycomes of Caenorhabditis elegans and other model organisms

Biochemical Society Symposium ◽

10.1042/bss0690117 ◽

2002 ◽

Vol 69 ◽

pp. 117-134 ◽

Cited By ~ 47

Author(s):

Stuart M. Haslam ◽

David Gems ◽

Howard R. Morris ◽

Anne Dell

Keyword(s):

Caenorhabditis Elegans ◽

Current Knowledge ◽

Structural Data ◽

Model Organisms ◽

Entire Genome ◽

C Elegans ◽

The Face ◽

Area Of Concern ◽

Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

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