cell cycle control
 
 
Condensin interacting genes
Systematic genetic analysis was carried out with various condensin mutants (the results for temperature sensitive ycs4-2 allele are shown).  Synthetic growth defects were scored at room temperature and verified by tetrad dissection.  
 
see Waples, WG et al, (2009) MBC for further details
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coordinating chromosome segregation and mitotic exit  Identification of new genes involved in condensin function While condensin is necessary for mitotic chromosome condensation from prophase through anaphase, it is not sufficient. My lab used both genomic and proteomic approaches to identify 30 new genes involved in higher-order chromosome dynamics (Waples et al, 2009; Yoon and Lavoie, in preparation) in addition to post-translational modifications of condensin required for its activity (Lavoie et al, 2004). Bill found that Tof2 is a novel regulator of mitotic exit and impacts condensin’s function in coordinating the exit from mitosis with the completion of chromosome segregation. He postulated that Tof2, which restrains the release of the key mitotic regulator, the phosphatase Cdc14, during early anaphase, establishes two cellular domains which differ in their potential for condensation. When Cdc14 is kept OFF, chromosome condensation car occur while Cdc14 activation correlates with chromosome decondensation. One project deriving from this work is to ask how Tof2 regulates the activity of Cdc14 phosphatase (which plays an essential role in resetting the cell cycle for the next growth phase). Our data suggests that Tof2 is an inhibitor of Cdc14 phosphatase release, but is it also an inhibitor of its enzymatic activity? There is controversy in the field, and we are continuing with this work—firstly by investigating how Tof2 regulates the Cdc14 phosphatase at the biochemical level (since we showed that the two proteins directly interact). In addition to this, it is noteworthy that the systematic genetic screen we performed for the AuroraB kinase Ipl1 in collaboration with Sue Biggins’ group (Fred Hutchinson Cancer Center) has recently been accepted for publication: Ng, TM, Waples, WG, Lavoie, BD and Biggins,S (2009) Pericentromeric sister chromatid cohesion promotes kinetochore biorientation, Mol Biol Cell, in press.