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DNA replication, synthesis of primer

Definition

Target type: biologicalprocess

The synthesis of a short nucleotide polymer using one strand of unwound DNA as a template. The product is usually a RNA molecule between 4-15 nucleotides long that provides a free 3'-OH that can be extended by DNA-directed DNA polymerases. In certain conditions, for example in response to DNA damage, some primases synthesize a DNA primer. [PMID:11395402, PMID:38203225, PMID:38492718]

DNA replication is a fundamental biological process that ensures the faithful duplication of the entire genome before cell division. This intricate process involves multiple steps and key enzymes, with the synthesis of primers being a crucial initial step.

Primers are short sequences of nucleotides, typically RNA, that provide a starting point for DNA polymerase to initiate DNA synthesis. DNA polymerase, the enzyme responsible for building new DNA strands, can only add nucleotides to an existing strand, and it cannot start a new chain from scratch.

The synthesis of primers is carried out by an enzyme called primase. Primase uses the parental DNA strand as a template to build a short RNA primer, typically 10-20 nucleotides long. This primer is complementary to the template strand and provides a free 3' hydroxyl group that DNA polymerase can recognize and bind to.

Once the primer is in place, DNA polymerase takes over and begins extending the primer by adding nucleotides that are complementary to the template strand. This process continues until the entire DNA molecule is replicated.

The synthesis of primers is essential for DNA replication because it provides the necessary starting point for DNA polymerase. Without primers, DNA polymerase would not be able to initiate DNA synthesis, and replication would not occur. The process of primer synthesis ensures that each daughter DNA molecule contains a complete and accurate copy of the parental DNA.

Here is a more detailed breakdown of the process:

1. **Origin Recognition:** Replication initiates at specific locations on the DNA molecule called origins of replication. These regions are recognized by proteins that bind to them and recruit other enzymes.

2. **Unwinding of DNA:** Once the origin of replication is recognized, the double-stranded DNA helix is unwound by an enzyme called helicase. This unwinding creates a replication fork, which is the Y-shaped structure where DNA synthesis occurs.

3. **Primer Synthesis:** Primase binds to the unwound DNA template strand and synthesizes a short RNA primer. This primer provides the necessary 3' hydroxyl group for DNA polymerase to initiate DNA synthesis.

4. **DNA Polymerase Activity:** DNA polymerase binds to the primer and begins extending it by adding nucleotides that are complementary to the template strand.

5. **Leading and Lagging Strand Synthesis:** DNA replication occurs simultaneously on both strands of the DNA molecule. The leading strand is synthesized continuously in the same direction as the unwinding of the DNA helix. The lagging strand, however, is synthesized in short fragments called Okazaki fragments, because it runs in the opposite direction of the unwinding. Each Okazaki fragment is initiated by a primer, and then extended by DNA polymerase.

6. **Primer Removal and Replacement:** Once the lagging strand is fully replicated, the RNA primers are removed by an enzyme called RNase H. The gaps left behind by the primers are then filled in by DNA polymerase, and the newly synthesized DNA fragments are joined together by an enzyme called DNA ligase.

7. **Termination:** DNA replication ends when the two replication forks meet at a specific termination site. This process ensures that the entire genome has been replicated.

In conclusion, the synthesis of primers is a critical step in DNA replication, providing the necessary starting point for DNA polymerase to initiate DNA synthesis. This process ensures the accurate and complete duplication of the entire genome before cell division.'
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Proteins (2)

ProteinDefinitionTaxonomy
DNA polymerase alpha catalytic subunitA DNA polymerase alpha catalytic subunit that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)
DNA-directed RNA polymerase, mitochondrialA DNA-directed RNA polymerase, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:O00411]Homo sapiens (human)

Compounds (9)

CompoundDefinitionClassesRoles
digallic aciddigallic acid: structure given in first sourcebenzoate ester;
gallate ester
foscarnetFoscarnet: An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV.

phosphonoformic acid : Phosphoric acid in which one of the hydroxy groups is replaced by a carboxylic acid group. It is used as the trisodium salt as an antiviral agent in the treatment of cytomegalovirus retinitis (CMV retinitis, an inflamation of the retina that can lead to blindness) and as an alternative to ganciclovir for AIDS patients who require concurrent antiretroviral therapy but are unable to tolerate ganciclovir due to haematological toxicity.
carboxylic acid;
one-carbon compound;
phosphonic acids
antiviral drug;
geroprotector;
HIV-1 reverse transcriptase inhibitor;
sodium-dependent Pi-transporter inhibitor
zidovudine triphosphate
resveratroltrans-resveratrol : A resveratrol in which the double bond has E configuration.resveratrolantioxidant;
phytoalexin;
plant metabolite;
quorum sensing inhibitor;
radical scavenger
TTPpyrimidine ribonucleoside 5'-triphosphate
aphidicolinaphidicolin : A tetracyclic diterpenoid that has an tetradecahydro-8,11a-methanocyclohepta[a]naphthalene skeleton with two hydroxymethyl substituents at positions 4 and 9, two methyl substituents at positions 4 and 11b and two hydroxy substituents at positions 3 and 9. An antibiotic with antiviral and antimitotical properties. Aphidicolin is a reversible inhibitor of eukaryotic nuclear DNA replication.

Aphidicolin: An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.
tetracyclic diterpenoidantimicrobial agent;
antimitotic;
antineoplastic agent;
antiviral drug;
apoptosis inducer;
Aspergillus metabolite;
DNA synthesis inhibitor;
EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor;
fungal metabolite
pnu183792PNU183792: structure in first source
GS-443902GS-441524 triphosphate: intracellular active metabolite of remdesivir

GS-443902 : An organic triphosphate that is GS-441524 in which the 5'-hydroxy group has been replaced by a triphosphate group. It is the active metabolite of remdesivir.
aromatic amine;
C-nucleoside;
nitrile;
organic triphosphate;
pyrrolotriazine
anticoronaviral agent;
antiviral drug;
drug metabolite
n(2)-(4-n-butylphenyl) 2'-deoxyguanosineN(2)-(4-n-butylphenyl) 2'-deoxyguanosine: RN & structure given in first source