An evolutionarily conserved role for separase in the regulation of nuclear lamins

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.

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Publication Details

Journal
Cell Death Discovery
Published
2025-10-21
DOI
https://doi.org/10.1038/s41420-025-02758-5
Primary Topic
Nuclear Structure and Function
Type
article
Field-Weighted Citation Impact
0.00

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article

An evolutionarily conserved role for separase in the regulation of nuclear lamins

Serena Rosignoli, Liliana Tullo, Michael L. Goldberg, C. Di Dio et al.
Cell Death Discovery
Nuclear Structure and Function
article

An evolutionarily conserved role for separase in the regulation of nuclear lamins

Serena Rosignoli, Liliana Tullo, Michael L. Goldberg, C. Di Dio, Chiara Borghi, Pascale Bertrand, Giuseppe Esposito, Gaëlle Pennarun, Alessandro Paiardini, Francesca Cipressa, Giuseppe Bosso, Giovanni Cenci, Nadia Schiralli
article en

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.

Cell Death DiscoveryVol. 11(1)
University of Modena and Reggio Emilia (IT), Università degli Studi della Tuscia (IT), Inserm (FR), Université Paris Cité (FR), Cornell University (US), Wellcome/MRC Cambridge Stem Cell Institute (GB), Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR), Université Paris-Saclay (FR), Istituto Superiore di Sanità (IT), Spanish National Cancer Research Centre (ES), CEA Paris-Saclay - Etablissement de Fontenay-aux-roses (FR), CEA Paris-Saclay (FR), Stem Cell Institute (PA), Institut de Radiobiologie Cellulaire et Moléculaire (FR), Istituto Pasteur (IT), Ferrari (Italy) (IT), Sapienza University of Rome (IT)
Institut National de la Santé et de la Recherche Médicale, Fondation ARC pour la Recherche sur le Cancer, Istituto Pasteur-Fondazione Cenci Bolognetti, Institut National Du Cancer, Université Paris-Saclay
Openalex Percentile: Top 73%
Nuclear Structure and Function
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