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Abstract
Centromeres and pericentromeres are specialized chromatin regions whose organization is critical for proper chromosome segregation through dynamic microtubule attachment. Smc5/6, highly enriched in pericentromeres, associates with microtubules. However, whether Smc5/6 contributes to chromatin folding and dynamics in these regions remains unclear. Here, we dissect Smc5/6 function at budding yeast centromeres by constructing smc5-2KE, a separation-of-function mutant that reduces microtubule binding by replacing two lysines (K624 and K631) at the Smc5 hinge with glutamic acid. After demonstrating reduced microtubule binding by smc5-2KE in vitro, we use high temporal resolution imaging in living cells and polymer modeling to show that Smc5/6 and microtubule binding restricts chromatin dynamics along chromosome arms, thus contributing to pericentromeric chromatin folding. The smc5-2KE mutant shows a strong pericentromere-specific reduction in homologous recombination repair, as well as defects in mitotic spindle length, centromere clustering and cytokinesis. Overall, our results reveal that Smc5/6-microtubule association ensures robust pericentromeric chromatin folding, contributing to genome integrity in the face of mitotic forces.
Competing Interest Statement
The authors have declared no competing interest.
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