telomere assembly

Definition

Target type: biologicalprocess

A cellular process that results in the aggregation, arrangement and bonding together of a set of components to form a telomere at a non-telomeric double-stranded DNA end. A telomere is a terminal region of a linear chromosome that includes telomeric DNA repeats and associated proteins. [GOC:mah, GOC:ns, PMID:11902675, PMID:8622671]

Telomere assembly is a complex biological process that ensures the proper replication and maintenance of chromosome ends. Telomeres are specialized DNA-protein structures that protect chromosomes from degradation and fusion, preventing the loss of genetic information during cell division. Here's a detailed description of the process:

1. **Synthesis of Telomeric DNA:** The enzyme telomerase, a reverse transcriptase, plays a crucial role in telomere assembly. It carries its own RNA template, which contains the sequence for telomere repeats. This RNA template serves as a guide for telomerase to add new telomeric repeats (TTAGGG in humans) to the 3' end of the lagging strand, extending it beyond the original length.

2. **Lagging Strand Replication:** During DNA replication, the lagging strand is synthesized discontinuously in short fragments called Okazaki fragments. Due to the nature of DNA polymerase, it cannot synthesize DNA at the very end of the lagging strand, leaving a gap. Telomerase fills this gap by adding telomeric repeats.

3. **Removal of RNA Primer:** The lagging strand synthesis involves an RNA primer, which is later removed by an enzyme called RNase H. This removal creates a short gap at the 5' end of the lagging strand.

4. **Filling the Gap:** The gap created after RNA primer removal is filled by DNA polymerase using the 3' end of the extended telomere as a template.

5. **Protection and Stabilization:** Telomeres are not only protected by their repetitive sequences but also by the association with specific proteins. These proteins form a protective cap that prevents the ends of chromosomes from being recognized as double-strand breaks, which could trigger DNA repair mechanisms or lead to chromosome fusion.

6. **Regulation of Telomere Length:** Telomere length is tightly regulated. In most somatic cells, telomerase activity is low, leading to gradual telomere shortening with each cell division. This shortening contributes to cellular aging and senescence. However, in germ cells and certain stem cells, telomerase activity is high, ensuring the maintenance of telomere length and the long-term viability of these cells.

7. **Telomere Dysfunction and Disease:** Shortening of telomeres is associated with various diseases, including cancer, aging-related disorders, and premature aging syndromes. Telomere dysfunction can contribute to genomic instability, cell senescence, and cell death.

In summary, telomere assembly is a critical process that ensures the stability and integrity of chromosomes. It involves the action of telomerase, DNA replication machinery, and specific proteins that protect and stabilize the telomere ends. The regulation of telomere length is crucial for cellular function, and its dysfunction can contribute to various diseases.'
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Proteins (1)

Compounds (1)