Duox-generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in <i>Drosophila</i> tracheoblasts.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34622778.
- Also identified by DOI 10.7554/eLife.68636 and PMC identifier 8594940.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Progenitors of the thoracic tracheal system of adult <i>Drosophila</i> (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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> in minutes. The findings presented reveal that H<sub>2</sub>O<sub>2</sub> activates ATR/Chk1 in tracheoblasts by a non-canonical, potentially direct, mechanism.
Medical subject headings
- Cell Cycle Proteins
- Checkpoint Kinase 1
- Drosophila Proteins
- Drosophila melanogaster
- Dual Oxidases
- G2 Phase Cell Cycle Checkpoints
- Protein Serine-Threonine Kinases
- Reactive Oxygen Species