SISTER CHROMATID COHESION 
 
 
MY CONTACT
Email: brigitte.lavoie@utoronto.ca
Address:
Dept of Molecular Genetics,
Medical Sciences Bld room 4278
1 King’s College Circle
Toronto, Ontario CANADA
M5S 1A8
 
PH  1-416-978-6123
FAX 1-416-978-6885
 
 
 
 
 
 
 
 
 
 
 
Image depicts a large budded yeast cell with precociously separated sister chromatids (green dots)
 
 
Condensin...compactor AND glue  My initial characterization of conditional condensin mutants revealed that mutants in different subunits exhibited different phenotypes, most notably in their cell cycle arrest points. My lab recently uncovered a hitherto unsuspected role for condensin in mitotic arm cohesion (Lam et al, 2006, GenesDev 20:2973). Wendy and Erica showed using cell cycle arrest mutants and microtubule depolymerizing drug nocodazole that condensin is required for sister chromatid cohesion during mitosis. They showed that condensin maintains pairing between sisters along chromosome arms, but does not appear to be required for cohesion at centromeric, telomeric or repetitive DNAs. This means two important things: (1) that the canonical cohesion activity, the cohesin complex, is not sufficient to keep sister chromatids robustly paired once the cells have progressed into metaphase; and (2) that condensin prevents aneuploidy not only by compacting chromosomes but also by pairing identical sisters. The discovery of a requirement for additional mechanisms of cohesion poses a number of exciting new questions. First, why is the cohesin complex no longer sufficient to keep sisters paired in metaphase? Has it been modified in some way as to downregulate its activity prior to anaphase onset or is there another activity that bolsters the cohesion function prior to mitosis which is turned off as cells enter metaphase? What factors are required for this downregulation? To address these questions, we have recently identified two new players in the regulation of mitotic cohesion. During her MSc in my lab, Kelly showed that these two factors can suppress the requirement for condensin based cohesion along chromosome arms. We propose a new model to explain the cell cycle regulation of sister chromatid cohesion. We are currently writing this up for publication. The next exciting questions that arise are how do these new factors do this? This is an exciting project in need of an enthusiastic student!