How does telomerase prevent linear chromosomes from shortening during replication?

From The School of Biomedical Sciences Wiki

A telomere can be defined as "The tip of a chromosome, containing a DNA sequence required for stability of the chromosome end". Telomeres are unique structures which may be present at the ends of linear chromosomes.

Genetic and microscopic observations first indicate that telomere, specialized DNA structure, serves to stabilize the chromosomes ends from shortening through progressive loss of DNA. As stated by Daniel et al.[1]. “In Drosophila, Herman J. Muller found that chromosomes without telomere end could not be recovered after chromosomes were broken by treatment with x-rays. In maize, Barbara McClintock observed that broken chromosomes frequently fused with one another and form new chromosomes with abnormal structures often having two centromeres.” It indicates that the presence of telomeres prevents chromosomes from losing base pair sequences at their ends and stop chromosomes from fusing to each other[2].

Contents

  • 1 Shortening of DNA
  • 2 The extension of telomere by telomerase
  • 3 The key to aging and cancer
  • 4 References

Shortening of DNA

During DNA replication, DNA polymerase enzyme requires an RNA primer in order to enable itself to copy DNA (DNA copied in a 5'→3' direction)[3]. Despite of the presence of DNA polymerase, there is a small part of the cell’s DNA can neither replicate nor repair[4]. Especially for the organisms with linear chromosomes, the fact that a DNA polymerase can add nucleotides only to the ends of 3’ end of the pre-existing DNA chain leads to a serious problem[5]. The usual replication provides no way to complete the 5’ ends of daughter DNA strands. Even when an Okazaki fragment can be started with an RNA primer bound to the very end of the template strand, once the primer is removed by exonuclease it cannot be replaced with DNA because there is no 3’ OH end that deoxynucleotides can be added to[1]. As a result, in each replication, the DNA molecules in a chromosome would become slightly shorter. This condition also refers as the end-replication problem[3]. Eukaryotes have solved the end-replication problem by locating highly repeated DNA sequence at the end, or telomeres, of each linear chromosome. In humans and other vertebrate organisms, the sequence of nucleotides in telomeres is TTAGGG, is repeated between 100 and 1000 times[5]. These non-coding sequences at the tips of the chromosomes ensure that the cells will not lose any important genetic function if the telomeres become shorter during every round of replication[5].

Most prokaryotes with circular genome do not have telomeres[1]. During DNA replication, the leading strand of circular chromosomes can simply continue to grow from 5’→3’ direction until its 3’ end is joined to the 5’ end of the lagging strand coming around from other direction[1]. On the lagging strand, the RNA primer for the last Okazaki fragment can be replaced by the free 3’OH end of the leading strand coming around in the opposite direction. [1]. In prokaryotes, the end-replication problem is solved by having circular DNA molecules as chromosomes[3].

Another cause of telomere shortening is oxidative stress[6]. This combination of the end replication problem and oxidative stress eventually causes the telomere to shorten to the point that the genome is exposed and the risk of apoptosis increases dramatically. This is believed to be the main cause of the hayflick limit in cells.

The extension of telomere by telomerase

The mechanism for restoring the ends of DNA molecule in a chromosome relies on telomerase. This enzyme works by adding tandem repeats of a simple sequence to the 3’ end of a DNA strand[3]. Hence, the loss of genomic sequences at each replication cycle can be compensated by addition of DNA sequence repeats[5]. In young cells, the telomerase function as protective caps to keep telomere from wearing down too much. However, there is eventually not enough of telomerase, as the cells divide repeatedly. Thus, the telomeres grow shorter and the cells age.

The key to aging and cancer

It is also suggested that the length of telomeres are linked to aging processes. Length of telomeres can also be affected by lifestyle and diet[7]. Aside from aging, telomeres have been said to play a role in oncogenesis, the increase in telomere length is a result of an inability of the cell to regulate the synthesis of telomerase, leading to overproduction[8]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Daniel L. Hartl, Maryellen Ruvolo,(2011) Genetic: analysis of genes and genomes, 8th edition, Burlington, Massachusetts: Jones & Bartlett Learning pg 246
  2. ↑ Borut Poljsak, The role of telomeres in skin ageing. Available at : https://www.novapublishers.com/catalog/product_info.php?products_id=34401 (last accessed 21.11.14)
  3. ↑ 3.0 3.1 3.2 3.3 Jeff Hardin, Gregory Bertoni, Lewis J. Kleinsmith (2011)Becker's world of the cell, 8th edition, San Francisco: Pearson Benjamin Cummings pg 564-565
  4. ↑ Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson (2010) Campbell Biology, 9th edition, San Francisco: Pearson Benjamin Cummings pg 364
  5. ↑ 5.0 5.1 5.2 5.3 Jeff Hardin, Gregory Bertoni, Lewis J. Kleinsmith (2011)Becker's world of the cell, 8th edition, San Francisco: Pearson Benjamin Cummings pg 564-565 Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson (2010) Campbell Biology, 9th edition, San Francisco: Pearson Benjamin Cummings pg 364-365
  6. ↑ von Zglinicki T.(2002) Oxidative stress shortens telomeres.27(7):339-44.
  7. ↑ Shammas MA. (2011)Telomeres, lifestyle, cancer, and aging.14(1):28-34.
  8. ↑ JW Shay, Y Zou, E Hiyama (2001)- Human molecular genetics.Oxford University Press.

How does telomerase help prevent the shortening of linear chromosomes?

That's where an enzyme called telomerase comes in. It's found in certain cells and helps prevent too much wear and tear. This includes shortening of your telomeres. Telomerase does this by adding additional telomere sequences to the ends of your chromosomes.

How does telomerase help prevent the shortening of linear chromosomes quizlet?

Telomerase prevents this shortening by adding/expanding telomeres.

What prevents the telomerase from over extending the ends of a linear chromosome?

Telomerase, an enzyme with a built-in RNA template, extends the ends by copying the RNA template and extending one end of the chromosome. DNA polymerase can then extend the DNA using the primer. In this way, the ends of the chromosomes are protected.

How linear chromosomes are shortened with replication?

Unlike bacterial chromosomes, the chromosomes of eukaryotes are linear. The ends of these chromosomes cannot be fully copied during replication, resulting in a slow, gradual shortening of the chromosome over subsequent replication cycles; this is known as the end-replication problem.