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

Cipressa, F.; Pennarun, G.; Bosso, G.; Rosignoli, S.; Tullo, L.; Schiralli, N.; Borghi, C.; Paiardini, A.; Goldberg, M. L.; Cenci, G.

doi:10.1101/2025.02.19.638993

bioRxiv · 10.1101/2025.02.19.638993

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

Cipressa, F.·Pennarun, G.·Bosso, G.·Rosignoli, S.·Tullo, L.·Schiralli, N.·Borghi, C.·Paiardini, A.·Goldberg, M. L.·Cenci, G.

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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. 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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Cipressa, F., Pennarun, G., Bosso, G., Rosignoli, S., Tullo, L., Schiralli, N., Borghi, C., Paiardini, A., Goldberg, M. L., Cenci, G.. 2025-02-21. An evolutionarily conserved role for separase in the regulation of nuclear lamins. https://doi.org/10.1101/2025.02.19.638993

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