Telomerase is a complex consisting of a protein called Tert and a short piece of RNA called Terc. Tert acts as a reverse transcriptase, while Terc acts as a template. The RNA template, which is rich in C, pairs with the G-rich, single-stranded 3′ end of telomeric DNA. The reverse transcriptase uses the RNA template to synthesize DNA in the usual 5′→3′ direction, thereby extending the already longer 3′ end. Telomerase then moves to the newly synthesized end and repeats the process. Once the G-rich strand is lengthened, the primase activity of DNA pol α can utilize it as a template to synthesize an RNA primer. This primer is then extended by DNA pol α and eventually removed by nucleases.

The length of telomeres is often considered as mitotic clocks since in most cells, their length is inversely related to the number of cell divisions that have occurred. The study of telomeres provides valuable insights into the biology of normal aging, premature aging diseases (progerias), and cancer.

Reverse transcriptases, like the one found in telomerase, are RNA-directed DNA pols. These enzymes play a role in the replication of retroviruses, including HIV. Retroviruses carry their genome in the form of single-stranded RNA molecules. Upon infecting a host cell, the viral enzyme reverse transcriptase uses the viral RNA as a template to synthesize viral DNA in the 5′→3′ direction. This DNA is then integrated into the host chromosomes. Reverse transcriptase activity is also observed in transposons, which are DNA elements capable of moving within the genome. In eukaryotes, most transposons are transcribed into RNA, which is used as a template for DNA synthesis by a reverse transcriptase encoded by the transposon. The resulting DNA is randomly inserted into the genome. Transposons that involve an RNA intermediate are referred to as retrotransposons or retroposons.

Nucleoside analogs that have been modified on the sugar portion can block DNA chain growth during replication. For instance, the incorporation of 2′,3′-dideoxyinosine (ddI) or conversion of the deoxyribose to another sugar like arabinose prevents further chain elongation. These compounds hinder the division of rapidly growing cells and viruses by impeding DNA replication. Cytosine arabinoside (cytarabine or araC) is commonly used in anticancer chemotherapy, while adenine arabinoside (vidarabine or araA) acts as an antiviral agent. Azidothymidine (AZT), also known as zidovudine (ZDV), terminates DNA chain elongation through substitution on the sugar moiety. It is worth noting that these drugs are generally supplied as nucleosides, which are then converted to nucleotides by cellular kinases.

A typical human somatic cell contains 46 chromosomes in its diploid state, with a total DNA length of approximately 2 meters. It may be challenging to comprehend how such a vast amount of genetic material can be effectively packaged within the limited volume of a cell nucleus, allowing for efficient replication and expression of genetic information. Achieving this requires the interaction of DNA with numerous proteins, each performing a specific function in the organized packaging of DNA molecules. Eukaryotic DNA is tightly bound to basic proteins called histones, which help order the DNA into fundamental structural units known as nucleosomes. Nucleosomes resemble beads on a string and further organize into more complex structures that condense and arrange the long DNA molecules into chromosomes, facilitating their segregation during cell division. The complex of DNA and protein within eukaryotic cell nuclei is referred to as chromatin.

Histones and nucleosomes play a crucial role in the formation of chromatin.
Telomerase: This complex contains a protein (Tert) that acts as a reverse transcriptase and a short piece of RNA (Terc) that acts as a template. The C-rich RNA template base-pairs with the G-rich, single-stranded 3′end of telomeric DNA (Fig. 30.24). The reverse transcriptase uses the RNA template to synthesize DNA in the usual 5′→3′ direction, extending the already longer 3′-end. Telomerase then translocates to the newly synthesized end, and the process is repeated. Once the G-rich strand has been lengthened, primase activity of DNA pol α can use it as a template to synthesize an RNA primer. The primer is extended by DNA pol α and then removed by nucleases.
Telomeres may be viewed as mitotic clocks in that their length in most cells is inversely related to the number of times the cells have divided. The study of telomeres provides insight into the biology of normal aging, diseases of premature aging (the progerias), and cancer.
D. Reverse transcriptases
As seen with telomerase, reverse transcriptases are RNA-directed DNA pols. A reverse transcriptase is involved in the replication of retroviruses, such as human immunodeficiency virus (HIV). These viruses carry their genome in the form of ssRNA molecules. Following infection of a host cell, the viral enzyme reverse transcriptase uses the viral RNA as a template for the 5′→3′ synthesis of viral DNA, which then becomes integrated into host chromosomes. Reverse transcriptase activity is also seen with transposons, DNA elements that can move about the genome (see p. 477). In eukaryotes, most transposons are transcribed to RNA, the RNA is used as a template for DNA synthesis by a reverse transcriptase encoded by the transposon, and the DNA is randomly inserted into the genome. [Note: Transposons that involve an RNA intermediate are called retrotransposons or retroposons.]
E. DNA replication inhibition by nucleoside analogs
DNA chain growth can be blocked by the incorporation of certain nucleoside analogs that have been modified on the sugar portion (Fig. 30.25). For example, removal of the hydroxyl group from the 3′-carbon of the deoxyribose ring as in 2′,3′-dideoxyinosine ([ddI] also known as didanosine), or conversion of the deoxyribose to another sugar, such as arabinose, prevents further chain elongation. By blocking DNA replication, these compounds slow the division of rapidly growing cells and viruses. Cytosine arabinoside (cytarabine, or araC) has been used in anticancer chemotherapy, whereas adenine arabinoside (vidarabine, or araA) is an antiviral agent. Substitution on the sugar moiety, as seen in azidothymidine (AZT), also called zidovudine (ZDV), also terminates DNA chain elongation. [Note: These drugs are generally supplied as nucleosides, which are then converted to nucleotides by cellular kinases.]
V. EUKARYOTIC DNA ORGANIZATION
A typical (diploid) human somatic cell contains 46 chromosomes, whose total DNA is ~2 m long! It is difficult to imagine how such a large amount of genetic material can be effectively packaged into a volume the size of a cell nucleus so that it can be efficiently replicated and its genetic information expressed. To do so requires the interaction of DNA with a large number of proteins, each of which performs a specific function in the ordered packaging of these long molecules of DNA. Eukaryotic DNA is associated with tightly bound basic proteins, called histones. These serve to order the DNA into fundamental structural units, called nucleosomes, which resemble beads on a string. Nucleosomes are further arranged into increasingly more complex structures that organize and condense the long DNA molecules into chromosomes that can be segregated during cell division. [Note: The complex of DNA and protein found inside the nuclei of eukaryotic cells is called chromatin.]
A. Histones and nucleosome formation