Esco1 and Esco2 regulate distinct cohesin functions during cell cycle progression

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Sister chromatid cohesion, mediated by the cohesin complex, is crucial for accurate chromosome segregation during cell division.
• Cohesin's ability to tether sister chromatids depends on the acetylation of its Smc3 subunit by Eco1 family acetyltransferases.
• Vertebrates have two Eco1 orthologs, Esco1 and Esco2, with largely unknown distinct functions in cohesion.

Purpose of the Study:

• To elucidate the specific roles of Esco1 and Esco2 in establishing and maintaining sister chromatid cohesion in vertebrate cells.
• To differentiate the contributions of Esco1 and Esco2 to the various functions of the cohesin complex.

Main Methods:

• Gene inactivation experiments targeting ESCO1 and ESCO2 in vertebrate cells.
• Analysis of Smc3 acetylation levels and their correlation with mitotic cohesion.
• Investigating the functional domains of Esco2 responsible for promoting cohesion.

Main Results:

• Sister chromatid cohesion establishment is critically dependent on Esco2 function.
• While Esco1 acetylates Smc3, its inactivation has minimal impact on mitotic cohesion.
• Esco2's role in cohesion is mediated by its N-terminal sequences, distinguishing it from Esco1.

Conclusions:

• Esco2 is the primary mediator of sister chromatid cohesion in vertebrates.
• Esco1-dependent Smc3 acetylation likely regulates non-cohesive cohesin activities, such as DNA repair and transcriptional control.
• Esco1 and Esco2 perform distinct and separable functions within the cohesin complex.