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Phosphoproteomics reveals a distinctive Mec1/ATR signaling response upon DNA end hyper-resection
Ethan J Sanford1, William J Comstock1, Vitor M Faça1,2
1Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
The EMBO Journal
|March 25, 2021
Summary
The Mec1/ATR kinase coordinates DNA repair by responding to DNA end resection. This study reveals how Mec1/ATR signaling regulates the STR complex, influencing homologous recombination outcomes.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- The Mec1/ATR kinase is vital for genome maintenance and DNA repair pathways.
- Its precise role in context-dependent signaling and homologous recombination (HR) remains incompletely understood.
Purpose of the Study:
- To investigate the specific Mec1/ATR signaling pathways activated by extensive DNA end resection.
- To elucidate the mechanisms by which Mec1/ATR regulates homologous recombination.
Main Methods:
- Phosphoproteomic analysis in budding yeast.
- Investigating protein-protein interactions and DNA repair assays.
Main Results:
- A unique Mec1/ATR signaling cascade triggered by hyper-resection was identified.
- Mec1/ATR phosphorylates the Sgs1-Top3-Rmi1 (STR) complex, promoting its interaction with Dpb11.
- Impaired HR-mediated repair was observed when Sgs1 was fused to Dpb11 phosphopeptide-binding domains.
Conclusions:
- Mec1/ATR signaling is specifically activated by extensive DNA end resection.
- Mec1/ATR-mediated phosphorylation of the STR complex is a key regulatory step influencing homologous recombination.
- This highlights the kinase's role in coordinating DNA repair and recombination.
