BioWorld International Correspondent

PARIS - French researchers at two cancer research and treatment centers discovered a second protein involved in the assembly of the nucleosome, the structure at the heart of the double helix of DNA.

The role of CAF-1 (chromatin assembly factor 1) in the regulation of the spatial organization of DNA is already well known, but now a second protein, HIRA (histone regulating protein), was found to play a part as well, operating through a completely independent pathway.

HIRA is known to interact with histones, the little proteins that form the nucleosome and contain additional information (the "histone code") that complements that contained in the genetic code. As part of their work aimed at discovering other proteins involved in the assembly of genetic material, researchers at the Institut Curie, a Paris-based cancer center, working in collaboration with the Institut Gustave-Roussy in Villejuif, France's leading cancer hospital, decided to investigate the possible role of the HIRA protein.

The genetic code of a human being contains about 3 billion cryptograms, and the spatial organization of the code within each cell is highly regulated. Within the nucleus, DNA is assembled in a structure called the chromatin, whose density makes it possible not only to store the genetic material but also to arrange it spatially. To ensure proper cellular function, the information contained in the DNA has to be available for "consultation" at any time, which requires the chromatin to be highly malleable and flexible. The slightest error in the 3-dimensional organization of genetic material can disorganize the genome, modify gene expression and cause malfunctions in the cell.

To determine whether the HIRA protein plays a role in DNA assembly, the researchers put it in contact with histones and a fragment of DNA and found that the DNA formed nucleosomes in vitro, indicating that it did play a role in the organization of the nucleosome. In further experiments, it was found that nucleosomes continued to form after the HIRA protein was removed, while the newly synthesized DNA continued to assemble itself, signifying that there was an independent pathway for nucleosome assembly specific to the HIRA protein and quite separate from that of CAF-1.

The exact role of the HIRA protein remains to be determined, however. The Institut Curie researchers are working on several hypotheses. One is that it might be a kind of quality-control agent checking the assembly work carried out by CAF1. Another is that it might be the guardian of certain DNA regions whose spatial organization has to be strictly maintained throughout the cell cycle.

That ongoing research is aimed at gaining a better understanding of the malfunctions that occur in the spatial organization of the genome, which could spawn new approaches to preventing and curing diseases caused by genetic alterations, especially cancer.

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