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Biological and Biochemical Foundations of Living Systems

DNA Replication

Mechanism of replication: separation of strands, specific coupling of free nucleic acids

Replicating a molecule of double-stranded DNA involves unwinding its helical structure, separating its two strands, and filling in new partner strands from free nucleic acids (nucleotides). Specific coupling assures that nucleotides are incorporated with correct base-pairing along the length of each of the separated strands (A with T, G with C).

Each of the separated strands is read and matched with appropriate nucleotides to create a newly synthesized partner strand. Nucleotides are added by attaching the phosphate group of the nucleotide (found on its 5′ carbon) to the open 3′ carbon on the end of the elongating strand. Thus replication proceeds by reading the original strand 3′ → 5′ and elongating the new strand 5′ → 3′.

Because the strands of double-stranded DNA run antiparallel, replication is performed in opposite directions, with one side extending its newly synthesized strand towards the replication fork and one side away. Only short portions (Okazaki fragments) can be synthesized in the direction away from the fork as it unzips, making this side the lagging strand. Replication on the leading strand, by contrast, is continuous into the direction of the replication fork as it unzips.

Semi-conservative nature of replication

DNA replication is semi-conservative on account of its two resulting molecules of double-stranded DNA each having retained a strand from the original molecule in addition to the newly synthesized strand.

Specific enzymes involved in replication

DNA helicaseworks at the replication fork to unwind the helix (unzips DNA)
Topoisomerases, including DNA gyraserelax super-coiling that results from unwinding the helix
Single-stranded binding proteins (SSBPs)bind to the separated strands of DNA to keep them from reannealing
Primasecreates short RNA primer that is temporarily attached for DNA polymerase to extend from
DNA polymerasefollows the replication fork, working to add new nucleotides in 5′ → 3′ direction; proofreads and removes incorrect nucleotides
DNA ligasehelps to anneal strands; joins Okazaki fragments
Telomeraselengthens telomeres of linear eukaryotic DNA

Origins of replication, multiple origins in eukaryotes

The process of DNA replication begins at an origin of replication, where the molecule's two strands are separated, producing a replication bubble with two replication forks unzipping the DNA bidirectionally away from the origin. Prokaryotes usually have a single origin of replication for their single, circular DNA. Eukaryotes, however, have multiple origins of replication across their numerous linear chromosomes.

Replicating the ends of DNA molecules

Linear chromosomes will arrive at an issue with replication at the ends of their lagging strands by which a portion of the strand at the very end (located in the telomere, a region of repetitive sequences at the end of the chromosome) is unable to be synthesized due to the lack of a 3′ end of a nucleotide to extend from. This issue results in the progressive shortening of the telomeres in linear chromosomes after numerous rounds of replication. The issue is resolved in presence of telomerase which acts to lengthen the telomeres with repetitive sequences, thereby protecting them from loss during replication.

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