I . DNA & RNA | 7. Telomeric repeat sequences: replication of the telomeric regions of eukaryotic chromosomes; functions and importance of the telomerase

Question 1

I. Telomeres
1. What is telomere?

Answer 1

A region of repetitive nucleotide sequence at each end of a chromosome, which protects the end of the chromosome from degeneration or from fusion with neighboring chromosomes.

Question 2

I. Telomeres
2. What is the role of telomere?

Answer 2

Important for stabilization of the chromosome and for preventing irregular recombination’s.

Question 3

I. Telomeres
3. What is Hayflick limit?

Answer 3

Telomeres are getting shorter and shorter upon each cell division, this shortening sets a limit on human lifespan (Hayflick limit)

Question 4

II. Structure of telomere:
1. Describe the structure of telomeres

Answer 4

• 10-15 kb sequences found at both ends of the chromosomes, composed of 1500 – 2000 tandem repeats (pattern of one or more nucleotides is repeated and the repetitions are directly adjacent to each other) of guanine rich TTAGGG hexanucleotide.
• There is also a telomere loop which is The overhang (a stretch of unpaired nucleotides in the end a DNA molecule) of the 3’ end.

Question 5

II. Structure of telomere:
2. Describe the structure and role of telomere loop

Answer 5

• The overhang (a stretch of unpaired nucleotides in the end a DNA molecule) of the 3’ end, form a loop called telomere loop, which disrupts the double helix at the end of the chromosome, because of sequence identity.
• The overhang displaces the complementary strand.
• The loop can bind and attract a sheltering complex, and this sheltering protects the end of the chromosome from fusion or degradation.

Question 6

III. Telomerase
1. How is the problem of telomere shortening solved?

Answer 6

The problem of telomere shortening is solved by an enzyme that adds telomeric (TEL) repeat sequences to the ends of each chromosome.
=> The enzyme is a protein-RNA complex called telomerase.

Question 7

III. Telomerase
2. What is the role of telomerase?

Answer 7

Telomerase expands the 3’ end
of chromosomes, has an RNA prosthetic group

Question 8

III. Telomerase
3A. How is the telomerase complex formed?

Answer 8

• telomerase reverse transcriptase (TERT) – which has reverse transcriptase activity. -> Polymerase enzyme that uses an RNA template to make a DNA strand
• telomerase RNA component (TERC) – serves as a template for telomere replication (ncRNA)
• RNA template (telomerase RNA)
• Subunits

Question 9

III. Telomerase
3B. What is the role of telomerase reverse transcriptase (TERT)?

Answer 9

The most important catalytic subunit is the TERT.
- It is responsible for catalyzing the addition of nucleotides in a TTAGGG sequence to the ends of a chromosome’s telomeres.

Question 10

III. Telomerase
3C. What is the role of telomerase RNA component (TERC)?

Answer 10

It serves as a template for telomere replication (ncRNA)

Question 11

III. Telomerase
4. Describe the structure of Telomerase

Answer 11

Telomerase has its own RNA to lengthen sequence but does not contain any information.

Question 12

III. Telomerase
5. Where do telomerases work?

Answer 12

Telomerases are capable of lengthening the telomeres (about 15 hexanucleotides per cell cycle).
=> They work only in embryonic stem cells, primordial germ line cells and cancer cells (its gene is epigenetically silenced in somatic cells).

Question 13

III. Telomerase
6. How is telomerases activated and inactivated?

Answer 13

Telomerase is usually inactivated by DNA-hyper methylation, but tumor cells can remove the methylation.

Question 14

III. Telomerase
7. What is the process of activating telomerases?

Answer 14

• Tumor/cancer cells de-methylate the promoter, so telomerase will be expressed, thus lengthen the telomeres causing immortality of the tumor cells
• For medical purpose (‘’in vitro’’), we use the advantage of expression of the telomerase in cell line (HeLa, cervical cancer cell)

Question 15

III. Telomerase
8. What are the consequences of inhibiting DNA synthesis in chemotherapy?

Answer 15

1. Inhibition of DNA-synthesis or nucleotide metabolism -> cells cannot be divided -> tumor therapy + antiviral medicines
2. Chemotherapy:
   - Tumor cells are divided quickly -> inhibition of the DNA- synthesis damages these cells more
   - Cells, which are divided physiologically quickly will also be damaged (GI-tract, bone marrow, hair) = side effects