Biology subjects

Gachet, Y.

Publications and source records attributed to Gachet, Y..

3 recordsLinked to original sources

bioRxiv2024

TORC1-dependent control of fission yeast cohesin

Cohesin is a DNA tethering complex essential for chromosome structure and function. In fission yeast, defects in the cohesin loader Mis4 result in chromosome segregation defects and dysregulated expression of genes near chromosome ends. A genetic screen for suppressors of the thermosensitive growth defect of mis4-G1487D identified several hypomorphic mutants of the Target of Rapamycin Complex 1 (TORC1), a conserved kinase that integrates cellular signals to regulate growth and metabolism through substrate-specific phosphorylation. Here, we demonstrate that the TORC1 pathway modulates cohesin functions in chromosome segregation and gene expression. In the context of compromised cohesin loading, the incidence of chromosome segregation defects was modulated by the growth medium in a TORC1-dependent manner. Pharmacological or genetic down-regulation of TORC1 activity restored cohesin binding to its chromosomal sites and improved mitotic chromosome segregation. Notably, reduced TORC1 activity also increased cohesin binding and chromosome transmission fidelity in wild-type cells. These results suggest that environmental cues influence chromosome stability via TORC1. Biochemically, TORC1 co-purified with cohesin and reduced TORC1 activity correlated with decreased phosphorylation of specific residues on Mis4 and cohesin. Mutations in cohesin that mimic the non-phosphorylated state mirrored the effects of TORC1 downregulation, showing that TORC1 is part of the network that controls cohesin phosphorylation to modulate its functions. Finally, we show that the functional interaction between TORC1 and Mis4 extends to the regulation of stress-responsive genes. Our findings reveal a TORC1-cohesin link that may facilitate cellular adaptation to environmental changes. Given that TORC1 inhibitors and calorie restriction extend lifespan in diverse species, this connection raises the intriguing possibility that cohesin-mediated changes in chromosome structure contribute to these effects.

molecular biology↗

bioRxiv2022

Condensin positioning at telomeres by Taz1 promotes telomere disjunction in anaphase

The localization of condensin along chromosomes is crucial for their accurate segregation in anaphase. Condensin is enriched at telomeres but how and for what purpose had remained elusive. Here we show that fission yeast condensin accumulates at telomere repeats through the balancing acts of Taz1, a core component of the shelterin complex that ensures telomeric functions, and Mit1, a nucleosome-remodeler associated with shelterin. We further show that condensin takes part in sister-telomere separation in anaphase, and that this event can be uncoupled from the prior separation of chromosome arms, implying a telomere-specific separation mechanism. Consistent with a cis-acting process, increasing or decreasing condensin occupancy specifically at telomeres modifies accordingly the efficiency of their separation in anaphase. Genetic evidence suggests that condensin promotes sister-telomere separation by counteracting cohesin. Thus, our results reveal a shelterin-based mechanism that enriches condensin at telomeres to drive in cis their separation during mitosis.

cell biology↗

bioRxiv2020

Aurora B and Condensin are dispensable for chromosome arm and telomere separation during meiosis II

In mitosis, while the importance of kinetochore-microtubule attachment has been known for many years, increasing evidence suggests that telomere dysfunctions also perturb chromosome segregation by contributing to the formation of chromatin bridges at anaphase. Recent evidence suggests that Aurora B ensures proper chromosome segregation during mitosis not only by controlling kinetochore-microtubule attachment but also by regulating telomere and chromosome arm separation. However, whether and how Aurora-B governs telomere separation during meiosis has remained unknown. Here, we show that fission yeast Aurora B localizes at telomeres during meiosis I and promotes telomere separation independently of the meiotic cohesin Rec8. In meiosis II, Aurora-B controls kinetochore-microtubule attachment but appears dispensable for telomere and chromosome arm separation. Likewise, condensin activity is nonessential in meiosis II for telomere and chromosome arm separation. Thus, in meiosis, the requirements for Aurora-B are distinct at centromeres and telomeres, illustrating the critical differences in the control of chromosome segregation between mitosis and meiosis II.

cell biology↗