PhD defense: Katrine Landvad

The role of the CRL4^Cdt2 target Spd1 in chromosome segregation in fission yeast

Supervisor: Professor Olaf Nielsen

Assessment Committee:
Professor Iain Hagan, University of Manchester
Head of Research, PhD, Søren Kjærulff, Chemometec A/S
Professor Michael Lisby, BIO (Chairman)

Abstract:
Ddb1, a component of the E3 ubiquitin ligase CRL4Cdt2, is needed for proper chromosome segregation as ddb1 deleted cells show unequal distribution of DNA to daughter cells and sensitivity to the microtubule destabilising drug TBZ. We show that Δddb1 cells have increased chromosome loss rates and that the CRL4 receptor protein Cdt2 is important for regulating Ddb1 activity in chromosome segregation. We further show that ddb1 deficiency results in premature disjunction of the sister chromatids and cause decreased protein levels of cohesion establishment factor Eso1. Deleting spd1, a known target of CRL4Cdt2, substantially reduces the observed defects, indicating that degradation of Spd1 is important to ensure proper chromosome segregation. Spd1 is degraded on PCNA and we propose that accumulation of Spd1 reduces access to PCNA, causing the observed chromosome segregation defects.