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S. cerevisiae Cells Can Grow without the Pds5 Cohesin Subunit.
Karan Choudhary1, Ziv Itzkovich1, Elisa Alonso-Perez1
1The Shmunis School of Biomedicine and Cancer Research, Tel Aviv Universitygrid.12136.37, Ramat Aviv, Israel.
Mbio
|June 16, 2022
Summary
Sister chromatid cohesion is maintained by cohesin, with Pds5 acting as a stabilizer. Compensating for Pds5 loss involves increasing Mcd1 levels and SUMO-modified PCNA on chromatin, crucial for DNA replication and chromosome segregation.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Sister chromatid cohesion (SCC) is essential for accurate chromosome segregation during cell division.
- The cohesin complex, comprising Smc1, Smc3, and Mcd1, is critical for establishing and maintaining SCC.
- Pds5 is an essential cohesin subunit whose precise function in SCC regulation remains incompletely understood.
Purpose of the Study:
- To investigate the function of the essential cohesin subunit Pds5 in regulating sister chromatid cohesion.
- To identify genetic strategies that can bypass the requirement for Pds5 function.
- To elucidate the interplay between Pds5, DNA replication factors, and cohesin dynamics.
Main Methods:
- Genetic screens were employed to identify high-copy-number suppressors and spontaneous mutants that allow survival in the absence of Pds5.
- Analysis of the effects of mutations in ELG1 (a PCNA unloader) and CLN2 (a G1 cyclin) on Pds5-deficient strains.
- Assessment of SUMO-modified PCNA (SUMO-PCNA) levels on chromatin and recruitment of the Srs2 helicase.
Main Results:
- Cells lacking Pds5 can survive if Mcd1 levels are elevated (e.g., via CLN2 mutations) and SUMO-PCNA accumulates on chromatin (due to ELG1 deletion).
- Elevated SUMO-PCNA promotes Srs2 helicase recruitment, leading to single-stranded DNA formation and enhanced cohesin loading.
- These findings suggest Pds5 has a dual role in stabilizing the cohesin ring and interacting with the DNA replication machinery.
Conclusions:
- Pds5 functions as a crucial stabilizer of the cohesin complex.
- Elevating Mcd1 levels and promoting SUMO-PCNA accumulation can compensate for the loss of Pds5.
- Pds5 is involved in coordinating DNA replication and sister chromatid cohesion establishment, highlighting its importance in cell cycle regulation.
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