New publication

Two negatives make a positive

Antagonists that are themselves antagonized play a common regulatory role in molecular biology. Peter Schlögelhofer, along with first author Ignacio Prusén Mota and their team, has now identified that the WAPL antagonist SORORIN is not confined to vertebrates but evolutionarily conserved, also to be found in Arabidopsis thaliana and Schizosaccharomyces pombe.  Furthermore, they obtained the first in vivo evidence that SORORIN antagonizes WAPL, which is in turn a cohesin antagonist. The study, published in Nature Communications in collaboration with the lab of Jan Michael Peters (Institute of Molecular Pathology), provides valuable insights into the molecular regulation of chromosome segregation in mitotic and meiotic cells.

Jul 01, 2024

During cell division, the cohesin protein complex ensures accurate chromosome segregation by maintaining chromatid cohesion. The Wings apart-like protein homolog (WAPL), releases cohesin from DNA by facilitating the opening of its ring-like structure. Group leader Peter Schlögelhofer explains, “Cohesin molecules must be tightly regulated to ensure the right amount is present at each stage of the cell cycle. Consequently, there are various mechanisms to remove it.” Proper cell division is crucial for the survival of all organisms, and evolutionary conserved in metazoans, requiring tight regulation of the entire process.

First author Ignacio ‘Nacho’ Prusén Mota explains: “Previous studies in vertebrates have shown that a protein called SORORIN antagonizes WAPL. While most cohesin regulators are conserved, SORORIN relatives remained elusive for many years.” To further investigate the regulation of cohesin in plants, the Schlögelhofer lab collaborated with Jan-Michael Peters (IMP), who previously elucidated the function of SORORIN in vertebrates and identified potential SORORIN relatives. Another collaborator is Juraj Gregan (University of Vienna), who investigates the role of SORORIN in plants and fission yeast. Consistent with its conservation across all kingdoms of life, the researchers discovered that SORORIN is essential for regular chromosome segregation in mitotic and meiotic cells.

The team demonstrated that there is an antagonistic interaction between SORORIN and WAPL – in other words, between a negative regulator and the regulator of that negative regulator. SORORIN phenotypes are severe but can be mitigated by deleting WAPL. The researchers also discovered that, in plant meiosis, SORORIN appears to protect sister centromere fusion independently of WAPL, suggesting that plant SORORIN has acquired additional functions.

Given the crucial role of plants in the world’s ecosystems, Peter advocates for intensified plant research: “We must fully understand the molecular mechanisms of cell division in plants to improve crop resilience and productivity. Unlike animals, plants cannot escape harsh conditions and are increasingly subjected to extreme conditions.” With climate change posing potential risks to crops and food security, basic plant research is essential.

About the study

DOI: 10.1038/s41467-024-49178-0

About the Schlögelhofer lab

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