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ATR takes a crack at the nuclear envelope
Marcus B Smolka1, Jan Lammerding2
1Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Molecular Cell
|October 20, 2023
Summary
The ATR kinase triggers nuclear envelope rupture by phosphorylating Lamin A/C. This process activates the cGAS-STING pathway, clears micronuclei, and may lead to cell death.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Nuclear envelope integrity is crucial for cellular function.
- Dysregulation of nuclear processes is linked to various diseases.
- The ATR kinase plays a role in DNA damage response.
Purpose of the Study:
- To investigate the role of ATR kinase in nuclear envelope rupture.
- To identify downstream effectors of ATR-mediated nuclear envelope rupture.
- To explore the implications of nuclear envelope rupture in cellular processes.
Main Methods:
- Western blotting to detect protein phosphorylation.
- Immunofluorescence microscopy to visualize nuclear structures.
- Cellular assays to assess pathway activation and cell death.
Main Results:
- ATR kinase phosphorylates Lamin A/C, a key component of the nuclear lamina.
- Phosphorylation of Lamin A/C by ATR promotes nuclear envelope rupture.
- ATR-mediated nuclear envelope rupture induces cGAS-STING pathway activation and micronuclei clearance.
Conclusions:
- ATR kinase is a critical regulator of nuclear envelope rupture.
- Phosphorylation of Lamin A/C is a key mechanism by which ATR induces nuclear envelope rupture.
- ATR-mediated nuclear envelope rupture has significant downstream consequences for cellular homeostasis and survival.
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