MOLECULAR MECHANISM OF MITOTIC CHROMOSOME CONDENSATION

 
 
 
 
 
 
 
 
 
 
 
 
 
MY CONTACT
 
University of Toronto
Dept of Molecular Genetics
Med Sci Blg #4278
1 King’s College Circle
Toronto Ontario Canada
M5S 1A8
TiDBITS:  YEAST PROJECTS
 
BRI’S 15 min PIZZA dough
 
1 cup All-purpose flour
1 cup whole wheat
2 tbsp instant YEAST  
1/2 tsp Salt
 
1 CUP V. HOT tap water
2 tbsp olive oil
 
mix the dry ingredients, then add the wet and stir to make stiff dough.  knead about 5 minutes on a lightly floured surface (may need 1/4 cup or so more flour).  
Cover with upturned bowl and let it rise 15 minutes while you get your pizza toppings ready.
 
stretch out the dough  and place in Pan (cast iron works great).  Top as desired and bake at 425F ~20 minutes.
 
faster than delivery!
 
Favorite combinations:
 
Tapenade, roasted peppers, spinach/basil and ricotta
 
Fresh Tomatoe, garlic, Mozzarella and Basil
 
Leftover grilled zucchini, eggplant, tomatoes with garlic and basill
 
 
 
 
 
 
How do condensins wrap it up?

Molecular intermediates in mitotic chromosome condensation
    The riddle of mitotic chromosome structure persists.  While the discovery of condensin was an important breakthrough, how condensin functions on mitotic chromatin to yield resolved and hightly compacted sister chromatids remains mysterious.  To begin to address this question, we monitored the condensation of an endogenous chromosomal locus, the large 1 Mb repetitive rDNA array on chromosome XII.  The rDNA is a known, bona fide target of condensin, and its homogenous character (it comprises of 100-150 repeats of a 9.1 kb region) means that small changes at the DNA level will be amplified at the ultrastructural level.  To monitor this, we used fluorescence in situ hybridization in budding yeast, we were the first to describe molecular intermediates in mitotic chromosome condensation in any organism. We identified distinct morphologies of condensing chromosomes and ordered the rDNA structures observed with respect to cell cycle progression. Using genetic and cell biological approaches to generate and characterize novel mutants in condensin, we showed that condensin is responsible for rDNA condensation from early M phase through anaphase, and used this as a benchmark against which to evaluate candidate genes for a role in mitotic chromosome condensation. 

















The use of cell cycle synchronized yeast as a model was instrumental in allowing us to (1) identify molecular intermediates in chromosome condensation, (2) uncover the existence of two cell cycle regulated condensation pathways, and (3) define the factors required for both metaphase and anaphase chromosome condensation.  The early (pre-anaphase) stage of condensation required condensin as well as cohesin, the sister chromatid cohesion machinery. Post-anaphase onset however, condensation becomes independent of cohesin whilst depending on both condensin and the conserved mitotic kinase, Ipl1 (AuroraB). 

	These data were published in a GenesDev paper from my lab (Lavoie, BD et al, 2004 In vivo re     quirements for rDNA chromosome condensation reveal two cell-cycle-regulated pathways for mitotic chromosome folding, GenesDev 18:76-87; also see  highlight in Nature Heinrichs, A 2004. Of a higher order, Nature 5:82).  Beyond this, the characterization of a deterministic mechanism for condensation led me to propose a multi-step model for rDNA condensation (Lavoie, BD. 2008 pRb and condensin--local control of global chromosome structure, GenesDev. 22:964-969).