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Biology subjects

Morlot, L.

Publications and source records attributed to Morlot, L..

2 recordsLinked to original sources

mnDINO: Accurate and robust segmentation of micronuclei with vision transformer networks

Recent advances in cell segmentation successfully produce models that generalize across various cell-lines and imaging types. However, these methods still fail to recognize subcellular structures such as micronuclei (MN), which are rare and tiny DNA-containing structures found outside of the main nucleus and observable under the microscope. While they can be hard to recognize in images, studying MN formation is of great interest because of their relationship to chromosome instability, genotoxicity, and cancer progression. Here we present a segmentation model, mnDINO, to segment micronuclei in DNA stained images under diverse experimental conditions with very high efficiency and accuracy. To train this model, we collected a heterogeneous set of images with more than five thousand annotated micronuclei. Trained with this diverse resource, the mnDINO model improves the accuracy of MN segmentation, and exhibits strong generalization across microscopes and cell lines. The dataset, code, and pre-trained model are made publicly available to facilitate future research in MN biology.

bioinformatics↗

Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation

Protein SUMOylation provides a principal driving force for cellular stress responses including DNA-protein crosslink (DPC) repair and arsenic-induced PML body degradation. In genome-scale screens, we identified the human E3 ligase TOPORS as a key effector of SUMO-dependent DPC resolution. We demonstrate that TOPORS promotes DPC repair by functioning as a SUMO-targeted ubiquitin ligase (STUbL) for DPCs, combining ubiquitin ligase activity through its RING domain with poly-SUMO chain binding via a cluster of SUMO-interacting motifs, analogous to the STUbL RNF4. Surprisingly, the STUbL activities of TOPORS and RNF4 are both required for SUMO-dependent DPC repair, PML degradation and other stress responses, making overlapping and distinct contributions to ubiquitin chain formation on SUMOylated targets to enable p97/VCP unfoldase recruitment. Combined loss of TOPORS and RNF4 is synthetic lethal even in unstressed cells, leading to defective clearance of SUMOylated proteins from chromatin accompanied by cell cycle arrest and apoptosis. Together, our findings establish TOPORS as a novel STUbL whose concerted action with RNF4 defines a general mechanistic principle in crucial cellular processes governed by direct SUMO-ubiquitin crosstalk. HighlightsO_LIThe RING E3 ligase TOPORS is required for SUMO-dependent DPC repair C_LIO_LITOPORS is a novel SUMO-targeted ubiquitin ligase (STUbL) C_LIO_LITOPORS promotes multiple STUbL-driven processes in conjunction with RNF4 C_LIO_LICombined TOPORS and RNF4 loss is synthetic lethal in human cells C_LI

molecular biology↗