Question

Cancer Biology

8. Re-expression of telomerase can confer immortality to emerging clones of tumor cells, and was originally viewed as an attractive target for drug discovery. However, which of the following best explains the lack of therapeutic efficacy for telomerase inhibitors? a. Telomerase alone is sufficient for transformation in human cells. b. Telomerase is required for the maintenance of somatic cell populations. c. Too many post-inhibition cell doublings would be required to see anti-tumor efficacy. d. Telomerase has sequence and biochemical similarities to viral reverse transcriptase. 9. Which of these is the most appropriate description of the end replication problem" that leads to telomere shortening and, ultimately, the finite lifespan (Hayflick Limit) of somatic cells? a. To block non-homologous end joining the replication complex stalls at the end and does not complete the strand. b. End replication occurs when two replication complexes collide and stall at chromosome ends. c. The use of RNA primers in transcription dictates that the newly transcribed end of each mRNA will be shortened by the length of the primer d. The use of RNA primers in DNA replication means that the newly synthesized end of each chromosome will be shortened by the length of the primer

Answer 1

Answer 1. (b) Telomerase require for maintenance of somatic cell population.

Telomerase is the enzyme responsible for maintenance of the length of telomeres by addition of guanine-rich repetitive sequences. Telomeres maintain genomic integrity in normal cells, and their progressive shortening during successive cell divisions induces chromosomal instability. In the large majority of cancer cells, telomere length is maintained by telomerase. Thus, telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors. So if inhibitor works properly, it will impact the functioning of normal somatic cell also.

Answer 2. (D)

Most of the time, primers of the Okazaki fragments can be easily replaced with DNA and the fragments connected to form an unbroken strand. When the replication fork reaches the end of the chromosome, however, there is a short stretch of DNA that does not get covered by an Okazaki fragment—essentially, there's no way to get the fragment started because the primer would fall beyond the chromosome end. Also, the primer of the last Okazaki fragment that does get made can't be replaced with DNA like other primers.

Because of this problem part of the DNA at the end of a chromosome goes uncopied in each round of replication, leaving a single-strand overhang