The Emerging Role of the Cytoskeleton in Chromosome Dynamics

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

The Emerging Role of the Cytoskeleton in Chromosome Dynamics

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

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

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

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

International audienceEukaryotic 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

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

Meeting reportBetween the first and tenth editions of this biannual rendezvous, yeasters were faced with an extraordinary revolution: Saccharomyces cerevisiae was indeed the first eukaryotic genome completely sequenced and released to the community, reviving its enormous potential for understanding life and opening the door to new approaches in biology. This revolution was immediately followed by ambitious programmes for sequencing the genomes of its distant cousins, e.g. the ‘Genolevures’ program held by a consortium of seven French laboratories, with the first aim of deciphering the different mechanisms of eukaryotic genome evolution over long periods of time. Taking advantage of the knowledge of these new genomes, researchers can now tackle much more easily relevant physiological studies in very different and distant yeasts, the diversity of which has once again been attractively represented at this 10th meeting. In addition to S. cerevisiae and Saccharomyces pombe still highly valued by researchers, many oral and written communications attested to the growing interest of our community for these ‘less-conventional’ yeasts. This explains why, in parallel with this genomic revolution, a mutation naturally occurred in the title of this meeting, with the recent emergence of three ‘s’ and subsequent transition from ‘Levure, Mode`le & Outil’ to ‘‘Levures, Mode`les & Outils’. This latest edition of LMO therefore brought together 250 participants from fields that rarely interact in order to discuss the current status of their research interests. This massive participation certified that our community remains very active, but also that it is particularly fond of this appointment. It offers a panoramic view of the extraordinary potential of yeasts, that continue to be driving forces in many fields of biology, from basic research to biotechnological challenges in coming years. Topics therefore ranged from a convincing demonstration of the central role of the mediator complex in RNA-polymerase II-dependent transcription to the engineering of new yeast strains to meet emerging energy problems that humanity will have to face in the near future. This report highlights some of the latest findings presented at this meeting, where two of the sessions were held in memory of renowned French colleagues Barbara Winsor and Pierre Thuriaux, who sadly passed away on the eve of retirement. 1. Beverages and energy: from ancestral use of yeasts to cutting edge biotechnological challenges2. Evolution and the genomics revolution3. Traffic and organelles: focus on mitochondrial ATP synthase4. Let’s travel into the nucleus: from DNA organisation to transcription5. RNA life, from synthesis to translation6. It’s all about control: key elements in cell cycle progression and establishment of cell polarit