FACT, quality control of the heart of chromosomes
The DNA “pellet” in the core of our cells is constantly forming and unforming. Knowing how DNA is structured and potentially inherited during cell divisions is a major challenge in biology.
Geneviève ALMOUZNI, PhD, directeur du Centre de Recherche
Geneviève Almouzni, Research Centre director at Institut Curie and her team Chromatin Dynamics (Institut Curie/CNRS/ PSL) have been studying histone chaperones for several years. To understand the importance of these proteins, we need to remember that histones are the bricks around which ADN coils to form chromatin. In the cell core, DNA is compacted to form chromosomes. Histone chaperones are proteins that accompany these histones to their destination to structure the chromatin. Just like an architect, these histone chaperones control assembly of the chromatin and its reorganisation when replicated, the repair or transcription of the DNA, at all key moments of cell life.
“Understanding how chromatin is placed and kept in place and how it changes constitutes one of the challenges of cellular biology”, explains Geneviève Almouzni. In this regard, her team has just made some progress in understanding these mechanisms by clarifying the role of one of these histone chaperones, FACT.
Its central role in the supply and dynamic of histones was already known, but its possible function in the centromere remained a mystery. The centromere is often considered to be the heart of the chromosome, and is the anchor point serving to guide the chromosomes during cell division. It has characteristic organisation in terms of its chromatin. The formation and maintenance of the centromere at each division is one of the keys to proper functioning of the cells, and involves specific factors known as CENP-T/W. The occurrence of errors in the centromere may compromise the equal separation of chromosomes between the two daughter cells. The division is then interrupted to attempt to repair, or the cell even self-destructs, and in the worst-case scenario, the “wrong” cell is preserved leading to the risk of development of cancer. The work of Geneviève Almouzni’s teams shows that these CENP-T/W factors resembling histones are organised by FACT, which makes sure they are placed precisely in the centromere. This mechanism, described for the first time, explains how FACT performs quality control of the centromere.
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The CENP-T/-W complex is a binding partner of the histone chaperone FACT.
Prendergast L, Müller S, Liu Y, Huang H, Dingli F, Loew D, Vassias I, Patel DJ, Sullivan KF, Almouzni G.
Genes Dev. 2016 Jun 1;30(11):1313-26. doi: 10.1101/gad.275073.115.