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CMG helicase disassembly is essential and driven by two pathways in budding yeast
Cristian Polo Rivera1, Tom D Deegan2,3, Karim P M Labib4
1MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
The EMBO Journal
|July 22, 2024
Summary
The CMG helicase (minichromosome maintenance helicase) disassembly is essential for cell viability. This study reveals ubiquitin-independent pathways involving Rrm3 and Pif1 helicases for CMG disassembly, crucial for genome stability.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- The CMG helicase is central to DNA replication in eukaryotes.
- CMG ubiquitylation and disassembly occur during replication termination.
- Existing evidence suggests convergent evolution of CMG ubiquitylation pathways.
Purpose of the Study:
- To investigate ubiquitin-independent pathways for CMG helicase disassembly.
- To determine if CMG disassembly is essential for cell viability.
- To elucidate the roles of Rrm3 and Pif1 helicases in CMG disassembly.
Main Methods:
- Reconstituted assays using budding yeast CMG.
- Generation of the mcm7-10R allele to compromise SCFDia2-mediated ubiquitylation.
- In vivo analysis of helicase disassembly, genome instability, and cell viability.
Main Results:
- The mcm7-10R mutation delays CMG disassembly and causes genome instability.
- Defective CMG ubiquitylation explains phenotypes of Dia2-deficient cells.
- Cell viability depends on Rrm3 and Pif1 helicases, indicating essential CMG disassembly.
Conclusions:
- CMG disassembly is essential for yeast cell viability.
- Rrm3 acts during S-phase to disassemble CMG complexes.
- Pif1-family helicases may have mediated CMG disassembly in early eukaryotes.
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