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Phosphorylation of CENP-R by Aurora B regulates kinetochore–microtubule attachment for accurate chromosome segregation
Divine Mensah Sedzro1,2 , Xiao Yuan1,2,* , McKay Mullen1,2,3 , Umer Ejaz1,2 , Tongtong Yang1,2 , Xu Liu1,2,3 , Xiaoyu Song1,2,3 , Yun-Chi Tang4 , Weijun Pan4 , Peng Zou5 , Xinjiao Gao1,2 , Dongmei Wang1,2 , Zhikai Wang1,2,3 , Zhen Dou1,2,* , Xing Liu1,2,3,* , Xuebiao Yao1,2,*
1MOE Key Laboratory for Cellular Dynamics, University of Science and Technology of China School of Life Sciences, Hefei 230027, China
2Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, National Center for Cross-Disciplinary Sciences & CAS Center for Excellence in Molecular Cell Science, Hefei 230026, China
3Morehouse School of Medicine, Atlanta, GA 30310, USA
4Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai 200031, China
5College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
*Correspondence to:Xiao Yuan , Zhen Dou , Xing Liu , Xuebiao Yao ,
J Mol Cell Biol, Volume 14, Issue 7, July 2022, mjac051,
Keyword: constitutive centromere-associated network (CCAN), kinetochore, microtubule, Aurora B, CENP-R, phosphorylation

Error-free mitosis depends on accurate chromosome attachment to spindle microtubules via a fine structure called the centromere that is epigenetically specified by the enrichment of CENP-A nucleosomes. Centromere maintenance during mitosis requires CENP-A-mediated deposition of constitutive centromere-associated network that establishes the inner kinetochore and connects centromeric chromatin to spindle microtubules during mitosis. Although previously proposed to be an adaptor of retinoic acid receptor, here, we show that CENP-R synergizes with CENP-OPQU to regulate kinetochore–microtubule attachment stability and ensure accurate chromosome segregation in mitosis. We found that a phospho-mimicking mutation of CENP-R weakened its localization to the kinetochore, suggesting that phosphorylation may regulate its localization. Perturbation of CENP-R phosphorylation is shown to prevent proper kinetochore–microtubule attachment at metaphase. Mechanistically, CENP-R phosphorylation disrupts its binding with CENP-U. Thus, we speculate that Aurora B-mediated CENP-R phosphorylation promotes the correction of improper kinetochore–microtubule attachment in mitosis. As CENP-R is absent from yeast, we reasoned that metazoan evolved an elaborate chromosome stability control machinery to ensure faithful chromosome segregation in mitosis.