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The [https://en.wikipedia.org/wiki/Negative_stain negative stain] electron microscopy (EM) structures of human and ''Tetrahymena'' telomerases were characterized in 2013.<sup id="cite_ref-11">[https://en.wikipedia.org/wiki/Telomerase#cite_note-11 [11]]</sup><sup id="cite_ref-12">[https://en.wikipedia.org/wiki/Telomerase#cite_note-12 [12]]</sup> Two years later, the first cryo-electron microscopy ([https://en.wikipedia.org/wiki/Cryo-EM cryo-EM]) structure of telomerase holoenzyme (''Tetrahymena'') was determined.<sup id="cite_ref-13">[https://en.wikipedia.org/wiki/Telomerase#cite_note-13 [13]]</sup> In 2018, the structure of human telomerase was determined through cryo-EM by UC Berkeley scientists.<sup id="cite_ref-14">[https://en.wikipedia.org/wiki/Telomerase#cite_note-14 [14]]</sup><br/> <br/> full text link : [https://en.wikipedia.org/wiki/Telomerase https://en.wikipedia.org/wiki/Telomerase]
=== DNA replicate ===
In [https://en.wikipedia.org/wiki/Molecular_biology molecular biology],<sup id="cite_ref-1">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-1 [1]]</sup><sup id="cite_ref-2">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-2 [2]]</sup><sup id="cite_ref-3">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-3 [3]]</sup> '''DNA replication''' is the [https://en.wikipedia.org/wiki/Biological_process biological process] of producing two identical replicas of DNA from one original [https://en.wikipedia.org/wiki/DNA DNA] molecule.<sup id="cite_ref-4">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-4 [4]]</sup> DNA replication occurs in all [https://en.wikipedia.org/wiki/Life living organisms] acting as the most essential part of [https://en.wikipedia.org/wiki/Heredity biological inheritance]. This is essential for cell division during growth and repair of damaged tissues, while it also ensures that each of the new cells receives its own copy of the DNA.<sup id="cite_ref-5">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-5 [5]]</sup> The cell possesses the distinctive property of division, which makes replication of DNA essential. DNA is made up of a [https://en.wikipedia.org/wiki/Nucleic_acid_double_helix double helix] of two [https://en.wikipedia.org/wiki/Complementary_DNA complementary] [https://en.wikipedia.org/wiki/DNA_strand strands]. The double helix describes the appearance of a double-stranded DNA which is thus composed of two linear strands that run opposite to each other and twist together to form.<sup id="cite_ref-6">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-6 [6]]</sup> During replication, these strands are separated. Each strand of the original DNA molecule then serves as a template for the production of its counterpart, a process referred to as [https://en.wikipedia.org/wiki/Semiconservative_replication semiconservative replication]. As a result of semi-conservative replication, the new helix will be composed of an original DNA strand as well as a newly synthesized strand.<sup id="cite_ref-7">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-7 [7]]</sup> Cellular [https://en.wikipedia.org/wiki/Proofreading_(Biology) proofreading] and error-checking mechanisms ensure near perfect [https://en.wikipedia.org/wiki/Fidelity fidelity] for DNA replication.<sup id="cite_ref-Berg_8-0">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-Berg-8 [8]]</sup><sup id="cite_ref-Alberts_9-0">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-Alberts-9 [9]]</sup> In a [https://en.wikipedia.org/wiki/Cell_(biology) cell], DNA replication begins at specific locations, or [https://en.wikipedia.org/wiki/Origin_of_replication origins of replication],<sup id="cite_ref-Hu_352.E2.80.93372_10-0">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-Hu_352–372-10 [10]]</sup> in the [https://en.wikipedia.org/wiki/Genome genome]<sup id="cite_ref-origins_11-0">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-origins-11 [11]]</sup> which contains the genetic material of an organism.<sup id="cite_ref-12">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-12 [12]]</sup> Unwinding of DNA at the origin and synthesis of new strands, accommodated by an [https://en.wikipedia.org/wiki/Enzyme enzyme] known as [https://en.wikipedia.org/wiki/Helicase helicase], results in [https://en.wikipedia.org/wiki/Replication_fork replication forks] growing bi-directionally from the origin. A number of [https://en.wikipedia.org/wiki/Protein proteins] are associated with the replication fork to help in the initiation and continuation of [https://en.wikipedia.org/wiki/DNA_synthesis DNA synthesis]. Most prominently, [https://en.wikipedia.org/wiki/DNA_polymerase DNA polymerase] synthesizes the new strands by adding [https://en.wikipedia.org/wiki/Nucleotide nucleotides] that complement each (template) strand. DNA replication occurs during the S-stage of [https://en.wikipedia.org/wiki/Interphase interphase].<sup id="cite_ref-13">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-13 [13]]</sup> DNA replication (DNA amplification) can also be performed ''[https://en.wikipedia.org/wiki/In_vitro in vitro]'' (artificially, outside a cell).<sup id="cite_ref-Jarillo-2021_14-0">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-Jarillo-2021-14 [14]]</sup> DNA polymerases isolated from cells and artificial DNA primers can be used to start DNA synthesis at known sequences in a template DNA molecule. [https://en.wikipedia.org/wiki/Polymerase_chain_reaction Polymerase chain reaction] (PCR), [https://en.wikipedia.org/wiki/Ligase_chain_reaction ligase chain reaction] (LCR), and [https://en.wikipedia.org/wiki/Transcription-mediated_amplification transcription-mediated amplification] (TMA) are examples. In March 2021, researchers reported evidence suggesting that a preliminary form of [https://en.wikipedia.org/wiki/Transfer_RNA transfer RNA], a necessary component of [https://en.wikipedia.org/wiki/Translation_(biology) translation], the biological synthesis of new [https://en.wikipedia.org/wiki/Protein proteins] in accordance with the [https://en.wikipedia.org/wiki/Genetic_code genetic code], could have been a replicator molecule itself in the very early development of life, or [https://en.wikipedia.org/wiki/Abiogenesis abiogenesis].<sup id="cite_ref-EL-20210302_15-0">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-EL-20210302-15 [15]]</sup><sup id="cite_ref-STD-20210403_16-0">[16]</sup><br/> ==== <sup id="cite_ref-STD-20210403_16-0">DNA Structure</sup> ==== DNA exists as a double-stranded structure, with both strands coiled together to form the characteristic [https://en.wikipedia.org/wiki/Double_helix double helix]. Each single strand of DNA is a chain of four types of [https://en.wikipedia.org/wiki/Nucleotide nucleotides]. Nucleotides in DNA contain a [https://en.wikipedia.org/wiki/Deoxyribose deoxyribose] sugar, a [https://en.wikipedia.org/wiki/Phosphate phosphate], and a [https://en.wikipedia.org/wiki/Nucleobase nucleobase]. The four types of [https://en.wikipedia.org/wiki/Nucleotide nucleotide] correspond to the four [https://en.wikipedia.org/wiki/Nucleobase nucleobases] [https://en.wikipedia.org/wiki/Adenine adenine], [https://en.wikipedia.org/wiki/Cytosine cytosine], [https://en.wikipedia.org/wiki/Guanine guanine], and [https://en.wikipedia.org/wiki/Thymine thymine], commonly abbreviated as A, C, G, and T. Adenine and guanine are [https://en.wikipedia.org/wiki/Purine pu]<sup id="cite_ref-17">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-17 [17]]</sup>[https://en.wikipedia.org/wiki/Purine rine] bases, while cytosine and thymine are [https://en.wikipedia.org/wiki/Pyrimidine pyrimidines]. These nucleotides form [https://en.wikipedia.org/wiki/Phosphodiester_bonds phosphodiester bonds], creating the phosphate-deoxyribose backbone of the DNA double helix with the nucleobases pointing inward (i.e., toward the opposing strand). Nucleobases are matched between strands through [https://en.wikipedia.org/wiki/Hydrogen_bonding hydrogen bonds] to form [https://en.wikipedia.org/wiki/Base_pair base pairs]. Adenine pairs with thymine (two hydrogen bonds), and guanine pairs with cytosine (three [https://en.wikipedia.org/wiki/Hydrogen_bonds hydrogen bonds]).<sup id="cite_ref-18">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-18 [18]]</sup> [https://en.wikipedia.org/wiki/Directionality_(molecular_biology) DNA strands have a directionality], and the different ends of a single strand are called the "3′ (three-prime) end" and the "5′ (five-prime) end". By convention, if the base sequence of a single strand of DNA is given, the left end of the sequence is the 5′ end, while the right end of the sequence is the 3′ end. The strands of the double helix are anti-parallel, with one being 5′ to 3′, and the opposite strand 3′ to 5′. These terms refer to the carbon atom in deoxyribose to which the next phosphate in the chain attaches. Directionality has consequences in DNA synthesis, because DNA polymerase can synthesize DNA in only one direction by adding nucleotides to the 3′ end of a DNA strand. The pairing of complementary bases in DNA (through [https://en.wikipedia.org/wiki/Hydrogen_bonding hydrogen bonding]) means that the information contained within each strand is redundant. Phosphodiester (intra-strand) bonds are stronger than hydrogen (inter-strand) bonds. The actual job of the phosphodiester bonds is where in DNA polymers connect the 5' carbon atom of one nucleotide to the 3' carbon atom of another nucleotide, while the hydrogen bonds stabilize DNA double helices across the helix axis but not in the direction of the axis.<sup id="cite_ref-19">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-19 [19]]</sup> This makes it possible to separate the strands from one another. The nucleotides on a single strand can therefore be used to reconstruct nucleotides on a newly synthesized partner strand.<sup id="cite_ref-20">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-20 [20]]</sup><br/> ==== <sup id="cite_ref-20">DNA polymerase</sup> ==== [https://en.wikipedia.org/wiki/DNA_polymerase DNA polymerases] are a family of [https://en.wikipedia.org/wiki/Enzyme enzymes] that carry out all forms of DNA replication.<sup id="cite_ref-22">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-22 [22]]</sup> DNA polymerases in general cannot initiate synthesis of new strands but can only extend an existing DNA or RNA strand paired with a template strand. To begin synthesis, a short fragment of RNA, called a [https://en.wikipedia.org/wiki/Primer_(molecular_biology) primer], must be created and paired with the template DNA strand. DNA polymerase adds a new strand of DNA by extending the 3′ end of an existing nucleotide chain, adding new [https://en.wikipedia.org/wiki/Nucleotide nucleotides] matched to the template strand, one at a time, via the creation of [https://en.wikipedia.org/wiki/Phosphodiester_bond phosphodiester bonds]. The energy for this process of DNA polymerization comes from hydrolysis of the [https://en.wikipedia.org/wiki/High-energy_phosphate high-energy phosphate] (phosphoanhydride) bonds between the three phosphates attached to each unincorporated [https://en.wikipedia.org/wiki/Nucleotide base]. Free bases with their attached phosphate groups are called [https://en.wikipedia.org/wiki/Nucleotide nucleotides]; in particular, bases with three attached phosphate groups are called [https://en.wikipedia.org/wiki/Nucleoside_triphosphate nucleoside triphosphates]. When a nucleotide is being added to a growing DNA strand, the formation of a phosphodiester bond between the proximal phosphate of the nucleotide to the growing chain is accompanied by hydrolysis of a high-energy phosphate bond with release of the two distal phosphate groups as a [https://en.wikipedia.org/wiki/Pyrophosphate pyrophosphate]. Enzymatic hydrolysis of the resulting [https://en.wikipedia.org/wiki/Pyrophosphate pyrophosphate] into inorganic phosphate consumes a second high-energy phosphate bond and renders the reaction effectively irreversible.<sup id="cite_ref-23">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-23 [Note 1]]</sup> In general, DNA polymerases are highly accurate, with an intrinsic error rate of less than one mistake for every 10<sup>7</sup> nucleotides added.<sup id="cite_ref-pmid18166979_24-0">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-pmid18166979-24 [23]]</sup> Some DNA polymerases can also delete nucleotides from the end of a developing strand in order to fix mismatched bases. This is known as proofreading. Finally, post-replication mismatch repair mechanisms monitor the DNA for errors, being capable of distinguishing mismatches in the newly synthesized DNA Strand from the original strand sequence. Together, these three discrimination steps enable replication fidelity of less than one mistake for every 10<sup>9</sup> nucleotides added.<sup id="cite_ref-pmid18166979_24-1">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-pmid18166979-24 [23]]</sup> The rate of DNA replication in a living cell was first measured as the rate of phage T4 DNA elongation in phage-infected ''E. coli''.<sup id="cite_ref-25">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-25 [24]]</sup> During the period of exponential DNA increase at 37 °C, the rate was 749 nucleotides per second. The mutation rate per base pair per replication during phage T4 DNA synthesis is 1.7 per 10<sup>8</sup>.<sup id="cite_ref-26">[https://en.wikipedia.org/wiki/DNA_replication#cite_note-26 [25]]</sup><br/> <br/>
