The process of DNA replication creates a particular problem for replicating the ends of linear
chromosomes.
1. Describe why the DNA replication machinery has difficulty replicating DNA ends.
2. Telomerase has been identified as an enzyme that can reverse the outcome of end replication.
Describe the near-universal mammalian chromosome telomere sequence and how telomerase
solves the problem of end replication.
Solution
Answer:
1. Describe why DNA replication machinery has difficulty replicating DNA ends:
Eukaryotic chromosomes are linear and not circular like bacterial chromosomes. The end of
eukaryotic chromosomes contains repetitive sequences (telomere) and cannot be fully copied
during each round of replication. DNA replication begins by unwinding of DNA double helix
and the synthesis of new strand by DNA polymerase. Since DNA polymerase can only work in a
unidirectional way (5’ to 3’) therefore one of the two new strands of DNA is synthesized
continuously (leading strand) and the other strand is synthesized in small stretches called as
Okazaki fragments (lagging strand). At the end of the lagging strand, since it is not possible to
attach an RNA primer, thererfore, the terminal region of chromosomes does not get covered by
Okazaki fragments. As a result, with each round of replication, the terminal chromosome
sequence cannot be copied leaving single stranded overhangs and gradual shortening of
chromosomes. This is called as “end replication problem”.
2. Describe Near Universal mammalian chromosome telomere sequence and how telomerase
solves the problem of end replication:
The termini of eukaryotic chromosome have specialized DNA caps called telomere which
comprise of short repetitive DNA sequence. Each time a cell divides some portion of the
telomere is lost.
Mammalian Telomere contains hundreds or thousands of tandem repeats of the same short DNA
sequence 5’-TTAGGG-3’. With each cell division telomeric sequence are lost thereby
protecting the critical chromosomal regions that contains gene.Telomerase (telomere terminal
transferase) is an RNA dependent DNA polymerase made up of RNA subunits and protein and is
involved in elongating the length of chromosome by extending the telomeres. Telomerase
enzyme binds to a special RNA molecule that contains a sequence complementary to the
telomeric repeat. By using the complementary RNA as a template, it extends the overhanging
strand of the telomere DNA. Since DNA polymerase cannot replicate the DNA sequence at the
end of the chromosomes therefore telomerase enzyme aids in terminal replication process by
attaching to the end of the chromosome. Absence of telomerase activity would result in
progressive shortening of chromosome with each cell division..
The process of DNA replication creates a particular problem for repl.pdf
1. The process of DNA replication creates a particular problem for replicating the ends of linear
chromosomes.
1. Describe why the DNA replication machinery has difficulty replicating DNA ends.
2. Telomerase has been identified as an enzyme that can reverse the outcome of end replication.
Describe the near-universal mammalian chromosome telomere sequence and how telomerase
solves the problem of end replication.
Solution
Answer:
1. Describe why DNA replication machinery has difficulty replicating DNA ends:
Eukaryotic chromosomes are linear and not circular like bacterial chromosomes. The end of
eukaryotic chromosomes contains repetitive sequences (telomere) and cannot be fully copied
during each round of replication. DNA replication begins by unwinding of DNA double helix
and the synthesis of new strand by DNA polymerase. Since DNA polymerase can only work in a
unidirectional way (5’ to 3’) therefore one of the two new strands of DNA is synthesized
continuously (leading strand) and the other strand is synthesized in small stretches called as
Okazaki fragments (lagging strand). At the end of the lagging strand, since it is not possible to
attach an RNA primer, thererfore, the terminal region of chromosomes does not get covered by
Okazaki fragments. As a result, with each round of replication, the terminal chromosome
sequence cannot be copied leaving single stranded overhangs and gradual shortening of
chromosomes. This is called as “end replication problem”.
2. Describe Near Universal mammalian chromosome telomere sequence and how telomerase
solves the problem of end replication:
The termini of eukaryotic chromosome have specialized DNA caps called telomere which
comprise of short repetitive DNA sequence. Each time a cell divides some portion of the
telomere is lost.
Mammalian Telomere contains hundreds or thousands of tandem repeats of the same short DNA
sequence 5’-TTAGGG-3’. With each cell division telomeric sequence are lost thereby
protecting the critical chromosomal regions that contains gene.Telomerase (telomere terminal
transferase) is an RNA dependent DNA polymerase made up of RNA subunits and protein and is
involved in elongating the length of chromosome by extending the telomeres. Telomerase
enzyme binds to a special RNA molecule that contains a sequence complementary to the
telomeric repeat. By using the complementary RNA as a template, it extends the overhanging
strand of the telomere DNA. Since DNA polymerase cannot replicate the DNA sequence at the
2. end of the chromosomes therefore telomerase enzyme aids in terminal replication process by
attaching to the end of the chromosome. Absence of telomerase activity would result in
progressive shortening of chromosome with each cell division.
