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Regulation of pericentromeric DNA loop size via Scc2-cohesin interaction
Sao Anh Nguyen1, Toyonori Sakata1,2, Katsuhiko Shirahige1,2
1Institute for Quantitative Biosciences, The University of Tokyo 1-1-1 Yayoi, Bunkyo-Ku, Tokyo 113-0032, Japan.
Iscience
|April 24, 2025
Summary
The deletion of ECO1 and WPL1 in yeast causes Scc2-cohesin to co-localize, enlarging DNA loops and delaying chromosome segregation. This highlights the cooperative regulation of cohesin by Wpl1 and Eco1 for proper chromosome function.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Cohesin mediates DNA loop extrusion, crucial for higher-order chromosome folding.
- The role and regulation of Scc2 (NIPBL) binding to cohesin on chromosomes are not fully understood.
- Most cohesins in budding yeast lack Scc2, indicating complex regulation.
Purpose of the Study:
- To investigate the regulation of Scc2-cohesin interaction on chromosomes.
- To determine the physiological consequences of altered Scc2-cohesin binding.
- To elucidate the cooperative roles of ECO1 and WPL1 in cohesin regulation.
Main Methods:
- Calibrated chromatin immunoprecipitation sequencing (ChIP-seq) in budding yeast.
- Genetic manipulation involving deletion of ECO1 and WPL1 genes.
- Analysis of Scc2-cohesin co-localization and DNA loop sizes.
Main Results:
- Deletion of both ECO1 and WPL1, but not individually, led to Scc2-cohesin co-localization in metaphase, especially near centromeres.
- Eco1's mitotic activity was essential to prevent Scc2-cohesin co-localization in the absence of WPL1.
- Scc2-cohesin co-localization resulted in enlarged pericentromeric DNA loops and delayed mitotic chromosome segregation.
Conclusions:
- Wpl1 and Eco1 cooperatively regulate Scc2-cohesin interactions.
- This regulation restricts pericentromeric DNA loop size.
- Proper regulation by Wpl1 and Eco1 is critical for timely chromosome segregation.
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