Non-random spatial organization of telomeres varies during the cell cycle and requires LAP2 and BAF

Debora Keller (1, 2) , Sonia Stinus (2) , David Umlauf (2) , Edith Gourbeyre (2) , Eric Biot (3) , Nicolas Olivier (1) , Pierre Mahou (1) , Emmanuel Beaurepaire (1) , Philippe Andrey (3) , Laure Crabbe (2)

1 LOB - Laboratoire d'Optique et Biosciences
2 MCD - Unité de biologie Moléculaire, Cellulaire et du Développement
3 IJPB - Institut Jean-Pierre Bourgin

Spatial genome organization within the nucleus influences major biological processes and is impacted by the configuration of linear chromosomes. Here, we applied 3D spatial statistics and modeling on high-resolution telomere and centromere 3D-structured illumination microscopy images in cancer cells. We found a multi-scale organization of telomeres that dynamically evolved from a mixed clustered-and-regular distribution in early G1 to a purely regular distribution as cells progressed through the cell cycle. In parallel, our analysis revealed two pools of peripheral and internal telomeres, the proportions of which were inverted during the cell cycle. We then conducted a targeted screen using MadID to identify the molecular pathways driving or maintaining telomere anchoring to the nuclear envelope observed in early G1. Lamina-associated polypeptide (LAP) proteins were found transiently localized to telomeres in anaphase, a stage where LAP2α initiates the reformation of the nuclear envelope, and impacted telomere redistribution in the next interphase together with their partner barrier-to-autointegration factor (BAF).

Mots clés: Chromosome organization; Membrane architecture; Molecular interaction.

Domaines: Biologie cellulaire; Modélisation et simulation; Traitement des images [eess.IV]; Imagerie

Debora Keller, Sonia Stinus, David Umlauf, Edith Gourbeyre, Eric Biot, et al.. Non-random spatial organization of telomeres varies during the cell cycle and requires LAP2 and BAF. iScience, 2024, 27 (4), pp.109343. ⟨10.1016/j.isci.2024.109343⟩. ⟨hal-04484063v2⟩