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Regulation of Pkc1 Hyper-Phosphorylation by Genotoxic Stress
Li Liu1, Jiri Veis2,3, Wolfgang Reiter2,4
1Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, MA 02118, USA.
Journal of Fungi (Basel, Switzerland)
|October 23, 2021
Summary
The cell wall integrity pathway
Area of Science:
- Cellular Biology
- Molecular Biology
- Genetics
Background:
- The cell wall integrity (CWI) pathway is known for cell wall biogenesis.
- It is also implicated in DNA damage response.
- Mpk1 (Slt2) activation by DNA damaging agents occurs independently of upstream CWI components.
Purpose of the Study:
- To investigate the role of Protein Kinase C (Pkc1) in genotoxic stress response.
- To elucidate the signaling pathway involving Pkc1, DNA damage checkpoint kinases, and casein kinase 1 (CK1).
- To determine Pkc1's contribution to the DNA damage transcriptional response.
Main Methods:
- Utilized SILAC mass spectrometry to identify Pkc1 phosphorylation sites.
- Generated Pkc1 mutants to assess the role of specific phosphorylation sites.
- Investigated protein-protein interactions between Pkc1, Hrr25, Mec1, and Tel1 under genotoxic stress.
Main Results:
- Pkc1 undergoes Mec1/Tel1-dependent hyper-phosphorylation upon genotoxic stress.
- Casein kinase 1 (CK1) ortholog Hrr25 associates with Pkc1, requiring Mec1 and Tel1.
- Hrr25 catalytic activity is essential for Pkc1 hyper-phosphorylation.
- Mutation of 13 CK1 consensus sites in Pkc1 blocked hyper-phosphorylation and affected RNR3 expression.
Conclusions:
- A novel pathway from DNA damage checkpoint kinases (Mec1, Tel1) to Pkc1 via Hrr25 is delineated.
- Pkc1's hyper-phosphorylation, regulated by Hrr25, is crucial for the DNA damage transcriptional response.
- Pkc1 plays a significant role in cellular responses to genotoxic stress beyond cell wall integrity.
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