Duox-generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in Drosophila tracheoblasts

Progenitors of the thoracic tracheal system of adult Drosophila (tracheoblasts) arrest in G2 during larval life and rekindle a mitotic program subsequently. G2 arrest is dependent on ataxia telangiectasia mutated and rad3-related kinase (ATR)-dependent phosphorylation of checkpoint kinase 1 (Chk1) t...

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Autores principales:	Amrutha Kizhedathu, Piyush Chhajed, Lahari Yeramala, Deblina Sain Basu, Tina Mukherjee, Kutti R Vinothkumar, Arjun Guha
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	Drosophila tracheoblasts G2 arrest ATR Chk1/grapes ROS Duox Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c6a6fa25a40c4c62b5490fb4d24957bd
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spelling	oai:doaj.org-article:c6a6fa25a40c4c62b5490fb4d24957bd2021-11-16T17:11:44ZDuox-generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in Drosophila tracheoblasts10.7554/eLife.686362050-084Xe68636https://doaj.org/article/c6a6fa25a40c4c62b5490fb4d24957bd2021-10-01T00:00:00Zhttps://elifesciences.org/articles/68636https://doaj.org/toc/2050-084XProgenitors of the thoracic tracheal system of adult Drosophila (tracheoblasts) arrest in G2 during larval life and rekindle a mitotic program subsequently. G2 arrest is dependent on ataxia telangiectasia mutated and rad3-related kinase (ATR)-dependent phosphorylation of checkpoint kinase 1 (Chk1) that is actuated in the absence of detectable DNA damage. We are interested in the mechanisms that activate ATR/Chk1 (Kizhedathu et al., 2018; Kizhedathu et al., 2020). Here we report that levels of reactive oxygen species (ROS) are high in arrested tracheoblasts and decrease upon mitotic re-entry. High ROS is dependent on expression of Duox, an H2O2 generating dual oxidase. ROS quenching by overexpression of superoxide dismutase 1, or by knockdown of Duox, abolishes Chk1 phosphorylation and results in precocious proliferation. Tracheae deficient in Duox, or deficient in both Duox and regulators of DNA damage-dependent ATR/Chk1 activation (ATRIP/TOPBP1/claspin), can induce phosphorylation of Chk1 in response to micromolar concentrations of H2O2 in minutes. The findings presented reveal that H2O2 activates ATR/Chk1 in tracheoblasts by a non-canonical, potentially direct, mechanism.Amrutha KizhedathuPiyush ChhajedLahari YeramalaDeblina Sain BasuTina MukherjeeKutti R VinothkumarArjun GuhaeLife Sciences Publications LtdarticleDrosophila tracheoblastsG2 arrestATRChk1/grapesROSDuoxMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Drosophila tracheoblasts G2 arrest ATR Chk1/grapes ROS Duox Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	Drosophila tracheoblasts G2 arrest ATR Chk1/grapes ROS Duox Medicine R Science Q Biology (General) QH301-705.5 Amrutha Kizhedathu Piyush Chhajed Lahari Yeramala Deblina Sain Basu Tina Mukherjee Kutti R Vinothkumar Arjun Guha Duox-generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in Drosophila tracheoblasts
description	Progenitors of the thoracic tracheal system of adult Drosophila (tracheoblasts) arrest in G2 during larval life and rekindle a mitotic program subsequently. G2 arrest is dependent on ataxia telangiectasia mutated and rad3-related kinase (ATR)-dependent phosphorylation of checkpoint kinase 1 (Chk1) that is actuated in the absence of detectable DNA damage. We are interested in the mechanisms that activate ATR/Chk1 (Kizhedathu et al., 2018; Kizhedathu et al., 2020). Here we report that levels of reactive oxygen species (ROS) are high in arrested tracheoblasts and decrease upon mitotic re-entry. High ROS is dependent on expression of Duox, an H2O2 generating dual oxidase. ROS quenching by overexpression of superoxide dismutase 1, or by knockdown of Duox, abolishes Chk1 phosphorylation and results in precocious proliferation. Tracheae deficient in Duox, or deficient in both Duox and regulators of DNA damage-dependent ATR/Chk1 activation (ATRIP/TOPBP1/claspin), can induce phosphorylation of Chk1 in response to micromolar concentrations of H2O2 in minutes. The findings presented reveal that H2O2 activates ATR/Chk1 in tracheoblasts by a non-canonical, potentially direct, mechanism.
format	article
author	Amrutha Kizhedathu Piyush Chhajed Lahari Yeramala Deblina Sain Basu Tina Mukherjee Kutti R Vinothkumar Arjun Guha
author_facet	Amrutha Kizhedathu Piyush Chhajed Lahari Yeramala Deblina Sain Basu Tina Mukherjee Kutti R Vinothkumar Arjun Guha
author_sort	Amrutha Kizhedathu
title	Duox-generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in Drosophila tracheoblasts
title_short	Duox-generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in Drosophila tracheoblasts
title_full	Duox-generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in Drosophila tracheoblasts
title_fullStr	Duox-generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in Drosophila tracheoblasts
title_full_unstemmed	Duox-generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in Drosophila tracheoblasts
title_sort	duox-generated reactive oxygen species activate atr/chk1 to induce g2 arrest in drosophila tracheoblasts
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/c6a6fa25a40c4c62b5490fb4d24957bd
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_version_	1718426326425141248

Duox-generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in Drosophila tracheoblasts

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