Year: 2025
Type: article
Abstract: Separase is a well-conserved endopeptidase that facilitates sister chromatid separation at the metaphase-anaphase transition by cleaving cohesins. Beyond its role in chromosome segregation, Separase also participates in various biological processes, including chromatin organization and replication, centrosome disengagement and duplication, cytokinesis, and telomere capping. Here, we report that the loss of Drosophila separase (Sse) function induces significant changes in global protein expression and affects the protein levels of both A/C-type lamin C (LamC) and B-type lamin Dm0 (Dm0). We further demonstrate that SSE physically interacts with lamins and colocalizes with them at the nuclear envelope during interphase. Additionally, loss of SSE activity disrupts nuclear organization in larval muscles and impairs locomotion in adult flies as a consequence of misregulation of LamC levels. Notably, similar to SSE in flies, depletion of human separase (ESPL1) in SV40 fibroblasts leads to misshapen nuclei and increased levels of lamin A. Moreover, we show that ESPL1 interacts with lamin A in human fibroblasts, suggesting that the functional interaction between Separase and lamins is evolutionarily conserved across different organisms.
Source: Cell Death Discovery
Institutions: Università degli Studi della Tuscia, Inserm, Université Paris Cité, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, CEA Paris-Saclay - Etablissement de Fontenay-aux-roses, Stabilité Génétique, Cellules Souches et Radiations, Service Cellules Souches et Radiation, Spanish National Cancer Research Centre, University of Modena and Reggio Emilia, Sapienza University of Rome, Istituto Superiore di Sanità, Cornell University, Istituto Pasteur
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: Institut National de la Santé et de la Recherche Médicale, Ministero dell’Istruzione, dell’Università e della Ricerca, Fondation ARC pour la Recherche sur le Cancer, Ligue Contre le Cancer, Istituto Pasteur-Fondazione Cenci Bolognetti, AFM-Téléthon, Institut National Du Cancer, Université Paris-Saclay
OpenAlex ID: W4415376965