Cohesin ATPase activities regulate DNA binding and coiled-coil configuration

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• The cohesin complex is essential for sister chromatid cohesion and genome compaction.
• Cohesin's coiled coils (CCs) can fold, bringing distant head and hinge domains together, but the role of ATPase activity in this process is unclear.

Purpose of the Study:

• To investigate the function of cohesin ATPase activities in cohesin dynamics.
• To understand how ATPase mutations affect chromosome segregation and cohesin structure.

Main Methods:

• Isolation and characterization of cohesin ATPase temperature-sensitive (ts) mutants in *Schizosaccharomyces pombe*.
• Screening for spontaneous suppressor mutations that rescue temperature lethality.
• Comprehensive saturation mutagenesis of identified suppressor hotspots.

Main Results:

• Both cohesin ATPase domains are essential for proper chromosome segregation.
• Suppressor mutations outside ATPase domains compensate for ATPase defects.
• Identified mutations suggest mechanisms for easier coiled coil folding, enhanced DNA binding, and altered coiled coil conformation.

Conclusions:

• Cohesin ATPase activities drive structural changes potentially involved in DNA packaging.
• Mutations outside ATPase domains can rescue cohesin ATPase defects through various structural alterations.