Cancer models in <i>Caenorhabditis elegans</i>

Kirienko, Natalia V.; Mani, Kumaran; Fay, David S.

doi:10.1002/dvdy.22247

Cited by 68 publications

(50 citation statements)

References 568 publications

(784 reference statements)

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“…NuRD machinery attenuate germline apoptosis: In C. elegans, the germ line is the only tissue to undergo apoptosis as a response to stress, making it an ideal system for the identification of genes involved in maintaining cellular homeostasis and promoting genetic integrity (Gartner et al, 2008;Kirienko et al, 2010). Our prior work revealed increased germline apoptosis in response to RNAi knockdown of several classes of chromatin remodelers, including the HDAC1 homolog hda-1 (Checchi and Engebrecht, 2011), which encodes a histone deacetylase that functions as part of a conserved, nucleosome remodeling and deacetylase (NuRD) complex (Passannante et al, 2010;Shi and Mello, 1998).…”

Section: Resultsmentioning

confidence: 99%

Maintenance of Genome Integrity by Mi2 Homologs CHD-3 and LET-418 in Caenorhabditis elegans

et al. 2018

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Meiotic recombination depends upon the tightly coordinated regulation of chromosome dynamics and is essential for the production of haploid gametes. Central to this process is the formation and repair of meiotic double-stranded breaks (DSBs), which must take place within the constraints of a specialized chromatin architecture. Here, we demonstrate a role for the nucleosome remodeling and deacetylase (NuRD) complex in orchestrating meiotic chromosome dynamics in Caenorhabditis elegans. Our data reveal that the conserved Mi2 homologs Chromodomain helicase DNA binding protein (CHD-3) and its paralog LET-418 facilitate meiotic progression by ensuring faithful repair of DSBs through homologous recombination. We discovered that loss of either CHD-3 or LET-418 results in elevated p53-dependent germline apoptosis, which relies on the activation of the conserved checkpoint kinase CHK-1. Consistent with these findings, chd-3 and let-418 mutants produce a reduced number of offspring, indicating a role for Mi2 in forming viable gametes. When Mi2 function is compromised, persisting recombination intermediates are detected in late pachytene nuclei, indicating a failure in the timely repair of DSBs. Intriguingly, our data indicate that in Mi2 mutant germ lines, a subset of DSBs are repaired by non-homologous end joining, which manifests as chromosomal fusions.We find that meiotic defects are exacerbated in Mi2 mutants lacking CKU-80, as evidenced by increased recombination intermediates, corpses, and defects in chromosomal integrity. Taken together, our findings support a model wherein the C. elegans Mi2 complex maintains genomic integrity through reinforcement of a chromatin landscape suitable for homology-driven repair mechanisms.4

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Section: Resultsmentioning

confidence: 99%

Maintenance of Genome Integrity by Mi2 Homologs CHD-3 and LET-418 in Caenorhabditis elegans

et al. 2018

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“…Since it was introduced as a genetic model organism [11], “the worm” has proven to be a powerful model that has served to provide seminal insights into a myriad of biological processes including development [12, 13], cancer [14], and aging [15]. C. elegans offers multiple unique advantages as a model organism, such as physiological simplicity (~1000 somatic cells), a short lifespan (~2 weeks), an early and short reproductive period, and hermaphroditic reproduction.…”

Section: Elegans As a Model Organismmentioning

confidence: 99%

Worms, bacteria, and micronutrients: an elegant model of our diet

Yılmaz

Walhout

2014

Trends in Genetics

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Micronutrients are required in small proportions in a diet to carry out key metabolic roles for biomass and energy production. Humans receive micronutrients either directly from their diet or from gut microbiota that metabolize other nutrients. The nematode Caenorhabditis elegans and its bacterial diet provide a relatively simple and genetically tractable model to study both direct and microbe-mediated effects of micronutrients. Recently, this model has been used to gain insight into the relationship between micronutrients, physiology and metabolism. In particular, two B-type vitamins, vitamin B12 and folate, have been studied in detail. Here we review how C. elegans and its bacterial diet provide a powerful interspecies systems biology model that facilitates the precise delineation of micronutrient effects and the mechanisms involved.

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“…The virtually invariant spatiotemporal cell division pattern can be experimentally exploited to detect subtle defects in the stringent control of cell divisions that result in ectopic cell production (van den Heuvel 2005; Kirienko et al 2010). Several tissues are particularly well suited for studies of developmental regulation of cell cycles.…”

mentioning

confidence: 99%

A Complex Regulatory Network Coordinating Cell Cycles DuringC. elegansDevelopment Is Revealed by a Genome-Wide RNAi Screen

Roy

Tobin

Memar

et al. 2014

G3 Genes|Genomes|Genetics

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The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development.

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Cancer models in Caenorhabditis elegans

Cited by 68 publications

References 568 publications

Maintenance of Genome Integrity by Mi2 Homologs CHD-3 and LET-418 in Caenorhabditis elegans

Maintenance of Genome Integrity by Mi2 Homologs CHD-3 and LET-418 in Caenorhabditis elegans

Worms, bacteria, and micronutrients: an elegant model of our diet

A Complex Regulatory Network Coordinating Cell Cycles DuringC. elegansDevelopment Is Revealed by a Genome-Wide RNAi Screen

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