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Acetylation of Nup62 by TIP60 ensures accurate chromosome segregation in mitosis
Hameed Akbar1,2 , Jun Cao1,2 , Dongmei Wang1,2 , Xiao Yuan1,2 , Manjuan Zhang1,2 , Saravanakumar Muthusamy3 , Xiaoyu Song1,3 , Xu Liu1,2 , Felix Aikhionbare3 , Xuebiao Yao1,2,* , Xinjiao Gao1,2,* , Xing Liu1,2,3,*
1MOE Key Laboratory for Cellular Dynamics and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
2CAS Center for Excellence in Molecular and Cell Sciences, Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, Hefei 230027, China
3Morehouse School of Medicine, Atlanta, GA 30310, USA
*Correspondence to:Xuebiao Yao , Xinjiao Gao , Xing Liu ,
J Mol Cell Biol, Volume 14, Issue 8, August 2022, mjac056,

Stable transmission of genetic information during cell division requires faithful mitotic spindle assembly and chromosome segregation. In eukaryotic cells, nuclear envelope breakdown (NEBD) is required for proper chromosome segregation. Although a list of mitotic kinases has been implicated in NEBD, how they coordinate their activity to dissolve the nuclear envelope and protein machinery such as nuclear pore complexes was unclear. Here, we identified a regulatory mechanism in which Nup62 is acetylated by TIP60 in human cell division. Nup62 is a novel substrate of TIP60, and the acetylation of Lys432 by TIP60 dissolves nucleoporin Nup62–Nup58–Nup54 complex during entry into mitosis. Importantly, this acetylation-elicited remodeling of nucleoporin complex promotes the distribution of Nup62 to the mitotic spindle, which is indispensable for orchestrating correct spindle orientation. Moreover, suppression of Nup62 perturbs accurate chromosome segregation during mitosis. These results establish a previously uncharacterized regulatory mechanism in which TIP60-elicited nucleoporin dynamics promotes chromosome segregation in mitosis.