In the cell nucleus, DNA wraps around what are called histone proteins, forming regularly spaced spherical bodies called nucleosomes. Thus, large portions of the genetic material are inaccessible to the gene reading machinery. Scientists at the German Cancer Research Center have now simulated at high time resolution how short DNA segments repeatedly detach spontaneously from the nucleosome. The group has been the first to demonstrate that the spool-shaped histone proteins have an active role in opening access to the genetic information.
Histones are evolutionary highly conserved proteins which are much the same in man, mouse or threadworm. They serve as coils around which the DNA molecule, a thread of several feet, wraps in the cell nucleus. Up until recent years, histones were believed to be little more than DNA packaging material. However, by now it is known that they also determine which genes are read and which are not read; thus, they actively participate in regulating many cell functions.
At DKFZ, Professor Dr. Jrg Langowski is studying the interactions of DNA and its "packaging" at a molecular level. "For DNA to be read it must be at least temporarily accessible. We wanted to find out how and, more importantly, for how long histones and DNA thread disassociate from their tightly wrapped state. This gives us a better understanding of how DNA is read and how this mechanism may possibly be disrupted in cancer cells," says Langowski, outlining the goal of his recently published research.
The packaging of DNA in the cell nucleus is extremely well studied: Each DNA spool consists of two molecules each of four different histone proteins. In each nucleosome, a DNA thread of 146 base pairs wraps around this spherical histone complex exactly 1.75 times. A small stretch of unwrapped DNA of variable length is followed by the next histone spool, forming a structure that looks like beads on a string. Prior studies have suggested that there
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Helmholtz Association of German Research Centres