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

## TL;DR

This paper shows that Separase, known for its role in cell division, also regulates nuclear lamins in flies and humans, affecting nuclear structure and function.

## Contribution

The study reveals an evolutionarily conserved role for Separase in regulating nuclear lamins across species.

## Key findings

- Loss of Drosophila separase (Sse) alters lamin protein levels and disrupts nuclear organization.
- Human separase (ESPL1) interacts with lamin A, indicating a conserved function.
- Misregulation of lamins due to Separase loss leads to impaired locomotion in flies and misshapen nuclei in human cells.

## 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.