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The way of putting together the centromere

Cell separates correctly during cell division and gives rise to two daughter cells with identical genetic material. A complex mechanism largely leads by a small region of the chromosome: the centromere, frequently described as the heart of the chromosome, and also at the heart of the research of Daniele Fachinetti and his team.  

The way of putting together the centromere

Division is an essential stage in the life of all cells: it participates in the body’s growth, wound repair, combating infection and in cell turnover. It plays also a key role during development. And when it goes wrong… the danger is real for the organism. If the various stages of cell division are not completed correctly, this can have damaging consequences for the daughter cells, including the initiation of tumor development. Among the various problems, one is the incorrect distribution of the chromosomes, the molecular basis of genetic heredity, within the two daughter cells, a phenomena called aneuploidy and typically observed in the majority of cancer cells.

“A correct balance of chromosome distribution following cell division is a prerequisite for normal development – says Daniele Fachinetti, head of the Molecular Mechanisms of Chromosome Dynamics team. Indeed, whole-chromosome aneuploidy is responsible for many human genetic diseases and cancer.”

Daniele Fachinetti and his team are exploring this key stage leading to the formation of two daughter cells with identical copy of genetic material and the different “molecular actors” involved. They mainly focus on the centromere, the anchor point that serve to guide the chromosomes during cell division.

In his last publication, Daniele Fachinetti's team described how the centromere forms and maintains during cell life and over divisions. The centromere is characterized at its most basic level by a specific pattern of chromatin organization, determined by the histones around which our DNA is wound: it can be identified by the presence of CENP-A, a variant of the canonical histone H3.

“Until now, CENP-A was considered to be always essential for centromere by maintaining its position and functionality – adds the biologist. To study this, we developed a new approach to allow rapid, inducible degradation of human CENP-A at every stage of the cell cycle.” Doing this, the researchers realize that after mediating the initial assembly of centromeric components then CENP-A become dispensable: another centromeric protein, CENP-B, the only DNA binding protein that bound to centromeric region, could “do the job” and make sure of the high fidelity chromosome segregation.

CENP-B is essential to preserve anchoring of the rails that lead chromosome segregation. “There is a reciprocal interdependency between centromeric chromatin marked by CENP-A and centromeric DNA bound by CENP-B in the maintenance of human chromosome segregation” concludes Daniele Fachinetti. This discovery shed new light on the cell division mechanism and the players involved necessary for our understanding of the genesis of chromosome instability.

Find out more

CENP-A is dispensable for mitotic centromere function after initial centromere/kinetochore assembly

Hoffmann S., Dumont M., Barra V., Ly P., Nechemia-Arbely Y., McMahon M.A., Hervé S., Cleveland D.W., Fachinetti D.

Cell Reports 17, 1–11, November 22, 2016

Avec Daniele Fachinetti, le centromère n’a qu’à bien se tenir

 

Texte : Céline Giustranti

Crédit photo : Marie Dumont - Daniele Fachinetti/Institut Curie

Mathilde Regnault
08/12/2016