Telomeres are small segments of DNA-protein complexes present at the ends of linear chromosomes of eukaryotic cells. Together with telomere-binding proteins, they constitute a special "hat" structure that maintains chromosome integrity and controls cell division cycles. Telomeres, centromeres, and origin of replication are the three major factors that keep chromosomes intact and stable. The length of telomeres reflects the history of cell replication and the potential for replication, and is known as the "mitotic clock" of cell life.
Figure 1. Schematic of telomeres.
Telomeres are short, multi-repeat non-transcribed sequences (TTAGGG) and some binding proteins that make up a special structure that, in addition to providing a buffer for non-transcribed DNA, protects chromosome ends from fusion and degradation, chromosomal localization, replication, It plays an important role in protecting and controlling cell growth and lifespan, and is closely related to apoptosis, cell transformation and immortalization. When the cells divide once, the telomeres of each chromosome will be shortened one by one. A part of the genes constituting the telomere are about 50 to 200 nucleotides, which cannot be completely replicated (lost) due to multiple cell divisions, so that the cells terminate their functions and no longer divide. Therefore, severely shortened telomeres are signals of cellular aging. In some cells that require an infinite replication cycle, the length of the telomere is retained by a specific DNA polymerase-telomerase that synthesizes telomeres after each cell division. Telomere DNA is composed of simple DNA highly repetitive sequences. Telomerase can be used to tail the telomeric DNA. Each time the DNA molecule is split, the telomere is shortened (such as the Okazaki fragment). Once the telomere is consumed, the telomere is consumed. The cells will immediately activate the apoptotic mechanism.
Telomeres, centromeres, and origin of replication are the three major factors that keep chromosomes intact and stable. At the same time, telomere is a special site for gene regulation, which often inhibits the transcriptional activity of genes located near telomeres (called telomere positional effect, TPE). In most eukaryotes, telomere elongation is catalyzed by telomerase. In addition, the recombination mechanism also mediates the elongation of telomeres. Telomerase, an enzyme responsible for the elongation of telomeres in cells, is a basic nuclear protein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes and fills the telomere lost by DNA replication. To make the telomere repair prolonged, the telomere will not be depleted due to cell division, and the number of cell divisions will increase. Telomeres play an important role in maintaining chromosomal stability and cell viability in cells of different species. Telomerase can prolong the shortening of telomeres (shortened telomeres have limited cell replication ability), thereby enhancing the proliferation of cells in vitro. The activity of telomerase in normal human tissues is inhibited and reactivated in tumors, which may be involved in malignant transformation. Telomerase plays an important role in maintaining telomere stability, genomic integrity, long-term cellular activity, and potential for continued proliferation. The existence of telomerase is to fill in the defects of DNA replication, that is, by prolonging the telomere repair, the telomere will not be depleted due to cell division, and the number of cell divisions will increase.
However, in normal human cells, telomerase activity is regulated very tightly, and active telomerase can be detected only in hematopoietic cells, stem cells, and germ cells, which must be constantly dividing. When the cells are differentiated and mature, they must be responsible for the needs of various tissues in the body, and each should perform their duties. Therefore, the activity of telomerase will gradually disappear. It is not important for cells to continue to divide themselves. Instead, differentiated and mature cells will carry a more important mission, which is to let the tissues and organs work and make life last.
Telomerase is an enzyme composed of a catalytic protein and an RNA template that synthesizes DNA at the end of a chromosome and confers immortality on cell replication.
Telomere DNA is composed of simple DNA highly repetitive sequences, and the chain at the end of the chromosome along the 5' to 3' direction is rich in GT. In yeast and humans, the telomere sequences are C1-3A/TG1-3 and TTAGGG/CCCTAA, respectively, and many.
The protein binds to the telomeric DNA.
The main functions of telomere DNA are:
First, the protected chromosome is not degraded by nucleases;
Second, prevent chromosomes from merging with each other;
Third, it provides a substrate for telomerase, which resolves the end of DNA replication and ensures complete replication of the chromosome.
Figure 2. Pattern of telomerase action.
Related genetic disease
Maintenance of telomere length is a prerequisite for continuous cell division. In cells that thrive or need to maintain their cleavage potential, such as germ cells, stem cells, and most cancer cells (~85%), telomerase is activated, which adds telomere sequences at the ends of telomeres to ensure these cells The stability of the mid-telomere length maintains the ability of the cells to continue to divide. The presence of highly homologous sequences in the subtelomeric region of the chromosome undergoes abnormal homologous recombination during meiosis, resulting in minor deletions, duplications, or translocations of chromosomes in the region, termed a subclonal recombination abnormality in the chromosome. Patients with this disease are mainly characterized by varying degrees of mental retardation, accompanied by growth retardation and deformities of various organs and systems.