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

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...

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Main Authors: Md Hashim Reza, Rashi Aggarwal, Jigyasa Verma, Nitesh Kumar Podh, Ratul Chowdhury, Gunjan Mehta, Ravi Manjithaya, Kaustuv Sanyal
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-04-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.3003069
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author Md Hashim Reza
Rashi Aggarwal
Jigyasa Verma
Nitesh Kumar Podh
Ratul Chowdhury
Gunjan Mehta
Ravi Manjithaya
Kaustuv Sanyal
author_facet Md Hashim Reza
Rashi Aggarwal
Jigyasa Verma
Nitesh Kumar Podh
Ratul Chowdhury
Gunjan Mehta
Ravi Manjithaya
Kaustuv Sanyal
author_sort Md Hashim Reza
collection DOAJ
description 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.
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spelling doaj-art-b169b7ee534f4fbfa2dfe1492623fef72025-08-20T02:26:27ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852025-04-01234e300306910.1371/journal.pbio.3003069Autophagy-related protein Atg11 is essential for microtubule-mediated chromosome segregation.Md Hashim RezaRashi AggarwalJigyasa VermaNitesh Kumar PodhRatul ChowdhuryGunjan MehtaRavi ManjithayaKaustuv SanyalEmerging 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.https://doi.org/10.1371/journal.pbio.3003069
spellingShingle Md Hashim Reza
Rashi Aggarwal
Jigyasa Verma
Nitesh Kumar Podh
Ratul Chowdhury
Gunjan Mehta
Ravi Manjithaya
Kaustuv Sanyal
Autophagy-related protein Atg11 is essential for microtubule-mediated chromosome segregation.
PLoS Biology
title Autophagy-related protein Atg11 is essential for microtubule-mediated chromosome segregation.
title_full Autophagy-related protein Atg11 is essential for microtubule-mediated chromosome segregation.
title_fullStr Autophagy-related protein Atg11 is essential for microtubule-mediated chromosome segregation.
title_full_unstemmed Autophagy-related protein Atg11 is essential for microtubule-mediated chromosome segregation.
title_short Autophagy-related protein Atg11 is essential for microtubule-mediated chromosome segregation.
title_sort autophagy related protein atg11 is essential for microtubule mediated chromosome segregation
url https://doi.org/10.1371/journal.pbio.3003069
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