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UMMS researchers answer century old question about 3D structure of mitotic chromosomes
Date:11/7/2013

distributed in the cell nucleus over a relatively large area. Previous work from Dekker and colleagues had shown that points of interaction along the chromosome influence gene expression and are the reason why different cell types are organized differently in three dimensions. But in order to separate and be distributed successfully to each daughter cell, the chromosomes need to be tightly condensed and neatly packaged for transport and transmission to daughter cells.

One set of theories posed that the long DNA molecules are coiled up hierarchically into successively thicker fibers to ultimately form the sausage-like mitotic chromosomes. An alternate set of models proposed that the DNA forms a series of loops that are then attached to a linear axial structure that forms the backbone of the chromosome.

Different lines of experimental evidence supported both models, preventing ruling either theory in or out. In order to isolate the 3D structure of the chromosome during metaphase, the authors used a combination of chromosome conformation capture technologies (3C, 5C and Hi-C) developed by the Dekker lab over the last decade to map the points of contact along the mitotic chromosome in different cell types synchronized to divide at the same time. The complex sets of data this yielded provided the backbone for understanding the three dimensional structure and spatial organization of these chromosomes.

Next, Dekker and the team, led by Leonid Mirny, PhD, associate professor at the Massachusetts Institute of Technology, developed sophisticated computer simulations using polymer models of the DNA molecule for the two competing theories for mitotic chromosome organization. Plugging each model into the simulation, Dekker, Mirny and colleagues found that their chromosome conformation capture data was inconsistent with the classical, hierarchical model. Instead, they found that during metaphase the chromosome was being packaged in a two phase process
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Contact: Jim Fessenden
james.fessenden@umassmed.edu
508-856-2000
University of Massachusetts Medical School
Source:Eurekalert

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