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  Section: General Biochemistry » Nucleic Acid Synthesis
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Replication of Telomeres—The End Game

Content of Nucleic Acid Synthesis
» Nucleic Acids
» Structure and Function of Nucleic Acids
    » Basic Chemical Structure
    » Base Pairing in Nucleic Acids: Double Helical Structure of Dna
    » Size, Structure, Organization, and Complexity of Genomes
    » Information Storage, Processing, and Transfer
    » Chromosomal Dna Compaction and Its Implications in Replication and Transcription
    » DNA Sequence and Chromosome Organization
    » Repetitive Sequences: Selfish DNA
    » Chromatin Remodeling and Histone Acetylation
» Nucleic Acid Syntheses
    » Similarity of DNA and RNA Synthesis
    » DNA Replication Vs Transcription: Enzymatic Processes
    » Multiplicity of DNA and RNA Polymerases
» DNA Replication and Its Regulation
    » DNA Replication
    » Regulation of DNA Replication
    » Regulation of Bacterial DNA Replication at the Level of Initiation
    » DNA Chain Elongation and Termination in Prokaryotes
    » General Features of Eukaryotic DNA Replication
    » Licensing of Eukaryotic Genome Replication
    » Fidelity of DNA Replication
    » Replication of Telomeres—The End Game
    » Telomere Shortening: Linkage Between Telomere Length and Limited Life Span
» Maintenance of Genome Integrity
» DNA Manipulations and their Applications
» Transcriptional Processes
    » Recognition of Prokaryotic Promoters and Role of S-Factors
    » Regulation of Transcription in Bacteria
    » Eukaryotic Transcription
    » RNA Splicing in Metazoans
    » Regulation of Transcription in Eukaryotes
    » Fidelity of Transcription (RNA Editing)
» Chemical Synthesis of Nucleic Acids (Oligonucleotides)
» Bibliography of Nucleic Acid Synthesis
Because DNA synthesis proceeds unidirectionally from 5´→3´ with respect to deoxyribose, by sequential addition of deoxynucleotides to the 3´ terminus of the deoxynucleotide added last, chain elongation can proceed to the terminus of the template strand oriented in the 3´ to 5´ direction. But how about synthesis of the terminus of the complementary strand ? Because synthesis of this discontinuous (lagging) strand occurs in the opposite direction by repeated synthesis of a primer, the terminus could not be replicated. This problem of end replication is eliminated in the circular genomes of bacteria and the small genomes of plasmids and viruses. However, in the case of linear eukaryotic chromosome, the problem is solved by a specialized mechanism of telomere replication. Telomeres are repeats of short G-rich sequences found at both ends of the chromosomes (Fig. 6). In the human genome, the telomere repeat unit is 5´ (T/A)m Gn 3´, where n>1 and 1< m < 4. Telomerase is a special DNA polymerase (reverse transcriptase) containing an oligoribonucleotide template 5´ Cn(A/T)m3´ (which is complementary to the telomere repeat sequence) as an integral part of the enzyme (Fig. 6). In the presence of other accessory proteins, telomerase utilizes its own template to generate the telomeric repeat unit and, by “slippage,” utilizes the same oligoribonucleotide template repeatedly to generate thousands of repeats of the same hexanucleotide unit sequence. Because the lagging strand terminal region does not require an external DNA template, the newly synthesized DNA is present in an extended single-stranded region. Telomeres provide a critical protective function to the chromosome by their unique structures and prevent their abnormal fusion.

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