69, The function of telomerase is

(1) Synthesis of DNA at ends of chromosome

(2) Synthesis at RNA primers

(3) Replication of normal DNA

(4) Reverse transcriptase of causing cancer

Introduction

Telomerase is a unique ribonucleoprotein enzyme complex that plays a crucial role in maintaining the integrity of eukaryotic chromosomes. Unlike typical DNA polymerases, telomerase possesses reverse transcriptase activity, enabling it to synthesize DNA at the very ends of linear chromosomes—known as telomeres. This function is vital for preventing chromosome shortening during DNA replication, a phenomenon that, if unchecked, leads to cellular aging and genomic instability.

The End-Replication Problem and Telomeres

During DNA replication, conventional DNA polymerases require a free 3′-OH group to extend a DNA strand. However, the lagging strand synthesis involves RNA primers that are later removed, leaving a gap at the very end of chromosomes. Because there is no upstream 3′-OH group to prime DNA synthesis at the chromosome terminus, the ends cannot be fully replicated, causing progressive shortening with each cell division—this is known as the end-replication problem.

To counteract this, eukaryotic chromosomes have repetitive DNA sequences called telomeres at their ends. Telomeres act as protective caps, preventing loss of essential genetic information and distinguishing chromosome ends from DNA breaks.

Telomerase Structure and Function

Telomerase is composed of:

• A catalytic protein subunit (TERT): A reverse transcriptase enzyme that synthesizes DNA using an RNA template.

• An intrinsic RNA component (TERC): Serves as the template for adding telomeric repeats.

• Accessory proteins: Assist in telomerase assembly and recruitment to telomeres.

Telomerase extends the 3′ overhang of telomeric DNA by reverse transcribing its RNA template into DNA repeats (e.g., TTAGGG repeats in humans). This elongation provides a template for conventional DNA polymerases to complete lagging strand synthesis, effectively restoring telomere length.

How Telomerase Solves the End-Replication Problem

1. Recognition of Telomere Ends:
   Telomerase binds specifically to the single-stranded 3′ overhang of telomeres.

2. Extension Using RNA Template:
   The RNA component within telomerase acts as a template to add repetitive DNA sequences to the 3′ end of the chromosome.

3. Completion of Lagging Strand:
   After telomerase elongates the leading strand template, DNA polymerase α synthesizes the complementary lagging strand DNA, filling in the gaps.

4. Telomere Length Maintenance:
   This process prevents telomere shortening, thereby maintaining chromosome stability and cellular lifespan.

Biological Significance of Telomerase Activity

• Genome Stability:
  Telomerase prevents chromosome ends from being recognized as DNA damage, avoiding unwanted repair processes like end-to-end fusions.

• Cellular Aging and Senescence:
  Most somatic cells have low or no telomerase activity, leading to gradual telomere shortening and eventual cellular senescence.

• Stem Cells and Germ Cells:
  Telomerase is active in these cells, allowing sustained proliferation and tissue regeneration.

• Cancer:
  Many cancer cells reactivate telomerase, enabling limitless replication potential and tumor progression.

Distinguishing Telomerase from DNA Polymerase

While both enzymes synthesize DNA, telomerase uniquely:

• Contains an RNA template to direct DNA synthesis.

• Extends only the ends of chromosomes (telomeres).

• Exhibits reverse transcriptase activity, synthesizing DNA from an RNA template.

• Is not involved in normal replication of the entire genome.

Summary Table

Conclusion

Telomerase is indispensable for maintaining chromosome integrity by synthesizing DNA at the ends of chromosomes, thereby solving the end-replication problem. Its unique reverse transcriptase activity and RNA template distinguish it from conventional DNA polymerases. By preserving telomere length, telomerase plays a critical role in cellular aging, genome stability, and cancer biology.

Keywords

telomerase, telomere synthesis, chromosome ends, end-replication problem, reverse transcriptase, RNA template, DNA polymerase, genome stability, cellular aging, cancer, telomere maintenance

Correct answer:
(1) Synthesis of DNA at ends of chromosome