Question

What will happen over time to a cell that is actively replicating but does not express telomerase? Explain your reasoning.

Answer 1

Ans.During DNA replication, the double stranded DNA is unwound and DNA polymerase synthesizes new strands. However, as DNA polymerase moves in a unidirectional manner (from 5’ to 3’), only the leading strand can be replicated continuously. In the case of the lagging strand, DNA replication is discontinuous. In humans small RNA primers attach to the lagging strand DNA, and the DNA is synthesized in small stretches of about 100-200 nucleotides, which are termed Okazaki fragments .The RNA primers are removed, replaced with DNA and the Okazaki fragments ligated together. At the end of the lagging strand, it is impossible to attach an RNA primer, meaning that there will be a small amount of DNA lost each time the cell divides. This ‘end replication problem’ has serious consequences for the cell as it means the DNA sequence cannot be replicated correctly, with the loss of genetic information.

• Telomeres are short nucleotide sequences found at the end of linear chromosomes which protect the genetic information. In vertebrates, telomeres have the hexameric sequence TTAGGG.
• telomeres are repeated hundreds to thousands of times at the end of the chromosomes. Each time cell division occurs, a small section of telomeric sequences are lost to the end replication problem, thereby protecting the genetic information.
• Telomeres can be restored by the enzyme telomerase, which extends telomeres length. Telomerase activity is found in cells that undergo regular division, such as stem cells and lymphocyte cells
• In normal cells that lack telomerase, cell division stops at the M1 stage due to the shortening of telomeres at each cell division stage and because of the consequent identification of uncapped telomeres as damaged DNA by P53 and p16/p Rb, and cellular senescence occurs.