Switch for telomerase
The main molecular switch providing telomere protection by the enzyme telomerase has been found
LifeSciencesToday based on the materials of the University of Illinois at Chicago:
UIC Study Identifies a Key Molecular Switch for Telomere Extension by Telomerase
Complementary binding of the protruding end of DNA to the matrix site of telomerase RNA
Telomerase builds up DNA, using its 3'-HE end as a seed,
and as a matrix – RNA, which is part of the enzyme.
This stage is called elongation. After that translocation takes place,
that is, the movement of DNA, elongated by one repeat, relative to the enzyme.
Scientists at the University of Illinois College of Medicine, Chicago, have for the first time described a key target of enzymes responsible for detecting DNA damage. For stable protection of the ends of chromosomes by the enzyme telomerase, which plays a central role in the development of cancer and in the aging process, this target must be chemically modified. The results of the study (Moser et al., Tel1ATM and Rad3ATR kinases promote Ccq1-Est1 interaction to maintain telomeres in fission yeast) are published online in the journal Nature Structural and Molecular Biology.
Telomeres are the end sections of chromosomes consisting of specialized DNA–protein structures that protect chromosomes and ensure their correct doubling in actively dividing cells.
Telomerase adds DNA repeats to the tail end of the telomere. It carries its own RNA. Human telomerase consists of 2 molecules of telomerase reverse transcriptase (TERT), 2 molecules of telomerase RNA (TERC) and 2 molecules of dyskerin. The two subunits of the enzyme are encoded by two different genes. TERT is a reverse transcriptase, that is, an enzyme that creates single–stranded DNA based on template single-stranded RNA. The diagram below corresponds to the structure of one catalytic telomerase subunit.
When telomeres become too short, the chromosomal ends are recognized as damaged. The control proteins responsible for checking the integrity of DNA are instructed to stop cell division, and DNA repair proteins are instructed to connect or rearrange the ends of chromosomes. Telomere dysfunction is associated by scientists with the formation of tumors and premature aging.
The research team led by Toru Nakamura, associate professor of the Department of Biochemistry and Molecular Genetics, focused on the contribution of two kinase enzymes, ATM and ATR, to the regulation of telomerase activity.
"Our study showed that ATM and ATR help to turn on the telomeric complex by chemically modifying a specific target protein associated with telomeric DNA, which then attracts telomerase in the same way that opened flowers attract bees with their bright colors," Nakamura comments on the results of the study.
The study was conducted on cells of budding yeast, a model organism that uses very similar protein complexes to human ones to maintain telomere length. Previous discoveries on yeast cells have given scientists crucial information that has helped identify several key factors needed to protect telomeres in human cells.
According to Nakamura, a similar ATM/ATR-dependent molecular switch regulating the protection of telomeres may also exist in human cells. However, some details of this mechanism may differ.
Since the violation of the mechanisms of regulation of telomere protection is a key factor in the formation of tumors, understanding how cellular components interact in the process of creating functional telomeres is very important for finding ways to prevent cancer.
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28.11.2011