Photo: NIH Image Gallery / Flickr
Australian biologists from the University of Sydney and University of New South Wales have identified a new mechanism that protects the telomeres from damage and prevents genomic instability that contribute to cancer. Preprint of a study published in the repository bioRxiv.
Telomeres are ends of chromosomes, consisting in man of TTAGGG repeats. They prevent the loss of genes during mitosis because DNA polymerase cannot synthesize a copy of DNA from the end, but every time replication is the shortening of the telomeres. When the telomeres become too short, cells age and die. Sometimes telomeres are the target of unwanted reparation (restoration) of DNA. In this case, different chromosomes can be “joined” with each other at their ends, or telomeres begin to uncontrollably increase, contributes to the emergence of immortal cancer cells.
It is known that at the ends of chromosomes have a protective structure called T-loop, which closes a circuit and block DNA repair mechanisms. The formation of T-loops is due to the enzyme TERF2 (Telomeric repeat-binding factor 2). This protein is a component of the complex shelterin, which directly binds to the telomeric DNA.
TERF2 prevent “stitching” telomeres via homologous end connection. The situation is complicated by the fact that TERF2 also inhibits protein kinase ATM, which is responsible for cell cycle arrest, has antitumor effects and does not produce as destructive DNA repair.
To understand how TERF2 finds a balance between the protection of telomeres and activation of ATM-dependent pathway, the researchers observed the formation of T-loops by using high-resolution microscopy. They have reduced activity TERF2 mouse and human chromosomes, which caused the unraveling of T-loops and the formation of the linear ends of chromosomes. Was activated ATM-path, however, the telomeres will still be protected from the ravages of “matching”, even when the mechanism of homologous compounds all were most active.
In the future, the researchers plan to establish whether age-related telomere shortening with less efficient formation of T-loops and activation of ATM.
Video, photo All from Russia.