Microtubule-dependent regulation of chromatin dynamics by the Smc5/6 complex
Abstract
Proper centromeres and pericentromeres folding is crucial for maintaining genome integrity and ensuring accurate chromosome segregation. Smc5/6 complex, which localizes at pericentromeres, can bind microtubules, yet its role in chromatin folding is unclear. Here, we investigate the functional relevance of Smc5/6 binding to microtubules in yeast using a separation-of-function mutant (smc5-2KE) that disrupt this interaction but leaves other biochemical activities of the complex intact. We demonstrate that Smc5/6 binding to microtubules constrains chromatin dynamics and regulates pericentromeric chromatin organization, as revealed by high-temporal-resolution imaging, polymer modeling, and in vitro approaches. Weakening of kinetochore activity in smc5 mutant cells leads to significant spindle defects and triggers the spindle checkpoint. Ultimately, the inability of Smc5/6 to associate effectively with microtubules and regulate pericentric chromatin compromise homologous recombination repair of DNA damage near centromeres. Overall, our findings indicate that Smc5/6-microtubules association preserves pericentromeric chromatin architecture and genome stability during mitosis.
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BibTeX
@article{carresimon2026microtubuledependent,
title = {{Microtubule-dependent regulation of chromatin dynamics by the Smc5/6 complex}},
author = {Ànnia Carré-Simon and Cecilia Martuzzi and Sarah Isler and Renaud Batrin and Henrik Dahl Pinholt and Timothy Földes and Guillaume Laflamme and Juan Reguera and Maria Barbi and Leonid Mirny and Damien D’amours and Emmanuelle Fabre},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.116943},
url = {https://hal.science/hal-05830488v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Microtubule-dependent regulation of chromatin dynamics by the Smc5/6 complex
AU - Ànnia Carré-Simon
AU - Cecilia Martuzzi
AU - Sarah Isler
AU - Renaud Batrin
AU - Henrik Dahl Pinholt
AU - Timothy Földes
AU - Guillaume Laflamme
AU - Juan Reguera
AU - Maria Barbi
AU - Leonid Mirny
AU - Damien D’amours
AU - Emmanuelle Fabre
PY - 2026
DA - 2026/10/21
JO - iScience
DO - 10.1016/j.isci.2026.116943
UR - https://hal.science/hal-05830488v1
AB - Proper centromeres and pericentromeres folding is crucial for maintaining genome integrity and ensuring accurate chromosome segregation. Smc5/6 complex, which localizes at pericentromeres, can bind microtubules, yet its role in chromatin folding is unclear. Here, we investigate the functional relevance of Smc5/6 binding to microtubules in yeast using a separation-of-function mutant (smc5-2KE) that disrupt this interaction but leaves other biochemical activities of the complex intact. We demonstrate that Smc5/6 binding to microtubules constrains chromatin dynamics and regulates pericentromeric chromatin organization, as revealed by high-temporal-resolution imaging, polymer modeling, and in vitro approaches. Weakening of kinetochore activity in smc5 mutant cells leads to significant spindle defects and triggers the spindle checkpoint. Ultimately, the inability of Smc5/6 to associate effectively with microtubules and regulate pericentric chromatin compromise homologous recombination repair of DNA damage near centromeres. Overall, our findings indicate that Smc5/6-microtubules association preserves pericentromeric chromatin architecture and genome stability during mitosis.
SN - 2589-0042
ER -