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Molecular & Cellular Biology

How chromosomes reorganize for cell division

Before a cell divides, it duplicates each chromosome. During most of the cell cycle, the two copies of each chromosome appear as a homogenous mass of chromatin within the cell nucleus. Only when cells begin to divide, a stage termed mitosis, each chromosome reorganizes its duplicated contents into two microscopically visible bodies termed sister chromatids. Sister chromatids remain connected until they correctly attach to the mitotic spindle, which is required for their correct distribution to daughter cells. Yet, some individual genomic sites move apart long before mitosis. How sister chromatid organization is regulated in time and to what extent it is influenced by the genomic neighborhood has been unclear.

To answer these questions, the Gerlich lab at IMBA engineered a collection of human cell lines to visualize endogenous genomic loci in distinct chromosomal regions. They imaged each cell line by 3D live-cell microscopy throughout an entire cell cycle to measure the distance between the duplicated copies of a specific genomic region. The team found that none of the investigated genomic sites remained permanently linked from chromosome duplication until entry into mitosis. Indeed, the distance between labelled sister loci during interphase was often as large as in mitotic chromosomes. However, unlike in mitosis where all genomic loci split to a roughly similar extent, the frequency of sister locus separation differed between different genomic regions. “These data suggest that the spatial organization of sister chromatids is governed by the chromosomal neighborhood,” says Daniel Gerlich.

By correlating their observations with public databases on chromosomal properties, the scientists found that genomic loci residing in inactive, late-replicating chromosomal regions separated their sisters less frequently than those residing in active and early-replicating regions. By following individual genomic sites, they discovered that sister loci separate early after replication and then remain at constant average distance while they move within dynamic chromatin polymers. The study hence reveals how duplicated chromosomes organize in a distinct pattern that matches the timing of DNA replication.

 

Original Paper:

Stanyte et al., The Journal of Cell Biology (2018) "Dynamics of sister chromatid resolution during cell cycle progression" has been published by The Journal of Cell Biology
This paper is available online at http://jcb.rupress.org/cgi/content/abstract/jcb.201801157.