Scientists of the Czeace University of the Western Reserve Area (US) discovered a previously unknown mechanism for the protection of DNA, which prevents genomic instability, premature aging and transformation of cells into cancer. It involves protein 53bp1, which has already been characterized as a molecule, restoring damaged genes. This is reported in the article published in the journal Nature Communication.
53bp1 protein is known for its important role in restoring DNA disappointment gaps, which represent a special danger to the cell due to the risk of genome reorganization. This compound stimulates a non-homologous connection of the ends (NHEJ) – the type of reparation of the DNA threads, in which the damaged ends “stap” directly. Although this more often leads to mutations than, for example, a homologous compound of the ends, the dysfunction of the mechanisms responsible for NHEJ leads to very difficult consequences for the cell until it is rebounded into the cancer.
Scientists found out that 53bp1 also interacts with a chromosome heterochromatin in a tightly packed state, which is why the genes contained in it are low-active. Heterochromatin maintains the structure of DNA and regulates the activity of genes, and its loss contributes to the destabilization of the genome and accelerated cell aging. An important role in the formation of heterochromatin plays protein HP1α.
It turned out that 53bp1 together with HP1α is subjected to a phase separation of the type of liquid-liquid. In the cell, it is responsible for the appearance of various non-memory structures in the form of “drops” of proteins and nucleotides and occurs when the connection concentration reaches the threshold values that allow the molecule to be addressed from the environment. Scientists have long noticed that proteins involved in the formation of heterochromatin are subjected to this process, but it was not clear whether the phase separation plays a direct role in the regulation of DNA and how precisely.
researchers blocked the 53bp1 functions and looked at how it affected heterochromatin. The deletion of the gene responsible for 53bp1 led to the reduction of heterochromatin centers and the restoration of the activity of “trash” DNA – tandem repetitions, that is, repetitive DNA sequences following each other. In heterochromatin, repeats are usually suppressed. Scientists also identified specific parts of the protein that participate in the phase division. Thus, some mutant form 53bp1, which are not capable of restoring cliffs in DNA, continued to adjust the heterochromatin packaging and protected cells from aging, which indicates the separation of functions between different parts of the molecule.