Publications by authors named "Maya Spichal"

5 Publications

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Germ granule dysfunction is a hallmark and mirror of Piwi mutant sterility.

Nat Commun 2021 03 3;12(1):1420. Epub 2021 Mar 3.

Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.

In several species, Piwi/piRNA genome silencing defects cause immediate sterility that correlates with transposon expression and transposon-induced genomic instability. In C. elegans, mutations in the Piwi-related gene (prg-1) and other piRNA deficient mutants cause a transgenerational decline in fertility over a period of several generations. Here we show that the sterility of late generation piRNA mutants correlates poorly with increases in DNA damage signaling. Instead, sterile individuals consistently exhibit altered perinuclear germ granules. We show that disruption of germ granules does not activate transposon expression but induces multiple phenotypes found in sterile prg-1 pathway mutants. Furthermore, loss of the germ granule component pgl-1 enhances prg-1 mutant infertility. Environmental restoration of germ granule function for sterile pgl-1 mutants restores their fertility. We propose that Piwi mutant sterility is a reproductive arrest phenotype that is characterized by perturbed germ granule structure and is phenocopied by germ granule dysfunction, independent of genomic instability.
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http://dx.doi.org/10.1038/s41467-021-21635-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930041PMC
March 2021

The meiotic phosphatase GSP-2/PP1 promotes germline immortality and small RNA-mediated genome silencing.

PLoS Genet 2019 03 28;15(3):e1008004. Epub 2019 Mar 28.

Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, United States of America.

Germ cell immortality, or transgenerational maintenance of the germ line, could be promoted by mechanisms that could occur in either mitotic or meiotic germ cells. Here we report for the first time that the GSP-2 PP1/Glc7 phosphatase promotes germ cell immortality. Small RNA-induced genome silencing is known to promote germ cell immortality, and we identified a separation-of-function allele of C. elegans gsp-2 that is compromised for germ cell immortality and is also defective for small RNA-induced genome silencing and meiotic but not mitotic chromosome segregation. Previous work has shown that GSP-2 is recruited to meiotic chromosomes by LAB-1, which also promoted germ cell immortality. At the generation of sterility, gsp-2 and lab-1 mutant adults displayed germline degeneration, univalents, histone methylation and histone phosphorylation defects in oocytes, phenotypes that mirror those observed in sterile small RNA-mediated genome silencing mutants. Our data suggest that a meiosis-specific function of GSP-2 ties small RNA-mediated silencing of the epigenome to germ cell immortality. We also show that transgenerational epigenomic silencing at hemizygous genetic elements requires the GSP-2 phosphatase, suggesting a functional link to small RNAs. Given that LAB-1 localizes to the interface between homologous chromosomes during pachytene, we hypothesize that small localized discontinuities at this interface could promote genomic silencing in a manner that depends on small RNAs and the GSP-2 phosphatase.
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http://dx.doi.org/10.1371/journal.pgen.1008004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456222PMC
March 2019

The Emerging Role of the Cytoskeleton in Chromosome Dynamics.

Front Genet 2017 19;8:60. Epub 2017 May 19.

Equipe Biologie et Dynamique des Chromosomes, Institut Universitaire d'Hématologie, CNRS UMR 7212, INSERM U944, Hôpital St. Louis 1Paris, France.

Chromosomes underlie a dynamic organization that fulfills functional roles in processes like transcription, DNA repair, nuclear envelope stability, and cell division. Chromosome dynamics depend on chromosome structure and cannot freely diffuse. Furthermore, chromosomes interact closely with their surrounding nuclear environment, which further constrains chromosome dynamics. Recently, several studies enlighten that cytoskeletal proteins regulate dynamic chromosome organization. Cytoskeletal polymers that include actin filaments, microtubules and intermediate filaments can connect to the nuclear envelope via Linker of the Nucleoskeleton and Cytoskeleton (LINC) complexes and transfer forces onto chromosomes inside the nucleus. Monomers of these cytoplasmic polymers and related proteins can also enter the nucleus and play different roles in the interior of the nucleus than they do in the cytoplasm. Nuclear cytoskeletal proteins can act as chromatin remodelers alone or in complexes with other nuclear proteins. They can also act as transcription factors. Many of these mechanisms have been conserved during evolution, indicating that the cytoskeletal regulation of chromosome dynamics is an essential process. In this review, we discuss the different influences of cytoskeletal proteins on chromosome dynamics by focusing on the well-studied model organism budding yeast.
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http://dx.doi.org/10.3389/fgene.2017.00060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437106PMC
May 2017

Evidence for a dual role of actin in regulating chromosome organization and dynamics in yeast.

J Cell Sci 2016 Feb 13;129(4):681-92. Epub 2016 Jan 13.

INSERM UMR 944, Equipe Biologie et Dynamique des Chromosomes, Institut Universitaire d'Hématologie, Hôpital St. Louis 1, Avenue Claude Vellefaux, Paris 75010, France CNRS, UMR 7212, Paris 75010, France Université Paris Diderot, Sorbonne Paris Cité, Paris 75010, France Institut Pasteur, Groupe Régulation Spatiale des Génomes, Paris 75015, France CNRS, UMR 3525, Paris 75015, France

Eukaryotic chromosomes undergo movements that are involved in the regulation of functional processes such as DNA repair. To better understand the origin of these movements, we used fluorescence microscopy, image analysis and chromosome conformation capture to quantify the actin contribution to chromosome movements and interactions in budding yeast. We show that both the cytoskeletal and nuclear actin drive local chromosome movements, independently of Csm4, a putative LINC protein. Inhibition of actin polymerization reduces subtelomere dynamics, resulting in more confined territories and enrichment in subtelomeric contacts. Artificial tethering of actin to nuclear pores increased both nuclear pore complex (NPC) and subtelomere motion. Chromosome loci that were positioned away from telomeres exhibited reduced motion in the presence of an actin polymerization inhibitor but were unaffected by the lack of Csm4. We further show that actin was required for locus mobility that was induced by targeting the chromatin-remodeling protein Ino80. Correlated with this, DNA repair by homologous recombination was less efficient. Overall, interphase chromosome dynamics are modulated by the additive effects of cytoskeletal actin through forces mediated by the nuclear envelope and nuclear actin, probably through the function of actin in chromatin-remodeling complexes.
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http://dx.doi.org/10.1242/jcs.175745DOI Listing
February 2016

10th Francophone Yeast Meeting 'Levures, Modèles & Outils'.

Res Microbiol 2012 Jun 31;163(5):309-15. Epub 2012 May 31.

Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés, INSA, CNRS UMR5504, INRA UMR792, Université de Toulouse, INSA, UPS, INP, 135 avenue de Rangueil, 31077 Toulouse cedex 4, France.

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http://dx.doi.org/10.1016/j.resmic.2012.05.007DOI Listing
June 2012