Smc5/6 - microtubules binding shapes pericentromeric chromatin
Carre-Simon, A.; Martuzzi, C.; Isler, S.; Batrin, R.; Dahl Pinholt, H.; Foldes, T.; Laflamme, G.; Barbi, M.; Mirny, L.; D'Amours, D.; Fabre, E.
Show abstract
Centromeres and pericentromeres are specialized chromatin regions essential for accurate chromosome segregation. Smc5/6, which localizes at pericentromeres, can bind microtubules, yet its role in chromatin folding is unclear. Here, we investigate the functional relevance of Smc5/6- microtubule binding in yeast, by targeting two lysines (K624, K631) within the Smc5 hinge domain known to mediate this binding. Using high-temporal-resolution imaging, polymer modelling, and in vitro approaches with a separation-of-function mutant smc5-2KE, we demonstrate that microtubules binding by Smc5/6 constrains chromatin dynamics and promotes pericentromeric folding. The smc5-2KE mutant, combined with a hypomorphic kinetochore mutant (Mtw1-3xGFP), leads to spindle and cytokinesis defects and triggers the spindle checkpoint. Furthermore, homologous recombination repair in pericentromeres is compromised. Overall, our findings indicate that Smc5/6 - microtubules association safeguard pericentromeric architecture and genome stability during mitosis.
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