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Autophagy-related protein Atg11 is essential for microtubule-mediated chromosome segregation

Md Hashim Reza, Rashi Aggarwal, Jigyasa Verma, Nitesh Kumar Podh, Ratul Chowdhury, Gunjan Mehta, Ravi Manjithaya and Kaustuv Sanyal

PLOS Biology, 2025, vol. 23, issue 4, 1-38

Abstract: Emerging studies hint at the roles of autophagy-related proteins in various cellular processes. To understand if autophagy-related proteins influence genome stability, we sought to examine a cohort of 35 autophagy mutants in Saccharomyces cerevisiae. We observe cells lacking Atg11 show poor mitotic stability of minichromosomes. Single-molecule tracking assays and live cell microscopy reveal that Atg11 molecules dynamically localize to the spindle pole bodies (SPBs) in a microtubule (MT)-dependent manner. Loss of Atg11 leads to a delayed cell cycle progression. Such cells accumulate at metaphase at an elevated temperature that is relieved when the spindle assembly checkpoint (SAC) is inactivated. Indeed, atg11∆ cells have stabilized securin levels, that prevent anaphase onset. Ipl1-mediated activation of SAC also confirms that atg11∆ mutants are defective in chromosome biorientation. Atg11 functions in the Kar9-dependent spindle positioning pathway. Stabilized Clb4 levels in atg11∆ cells suggest that Atg11 maintains Kar9 asymmetry by facilitating proper dynamic instability of astral microtubules (aMTs). Loss of Spc72 asymmetry contributes to non-random SPB inheritance in atg11∆ cells. Overall, this study uncovers an essential non-canonical role of Atg11 in the MT-mediated process of chromosome segregation.Autophagy-related proteins have roles in several cellular processes, but their function in genome stability remains unclear. Here, the authors show that Atg11 has an essential non-canonical function in error-free chromosome segregation via the Kar9-dependent spindle positioning pathway.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pbio00:3003069

DOI: 10.1371/journal.pbio.3003069

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