Page last updated: 2024-10-24

lagging strand elongation

Definition

Target type: biologicalprocess

The process in which an existing DNA strand is extended in a net 3' to 5' direction by activities including the addition of nucleotides to the 3' end of the strand, complementary to an existing template, as part of DNA replication. Lagging strand DNA elongation proceeds by discontinuous synthesis of short stretches of DNA, known as Okazaki fragments, from RNA primers; these fragments are then joined by DNA ligase. Although each segment of nascent DNA is synthesized in the 5' to 3' direction, the overall direction of lagging strand synthesis is 3' to 5', mirroring the progress of the replication fork. [GOC:mah, ISBN:071673706X, ISBN:0815316194]

Lagging strand elongation is a fundamental process in DNA replication, ensuring the complete copying of the entire genome. It involves the synthesis of a new DNA strand in a discontinuous manner, opposite to the leading strand. Here's a detailed breakdown:

1. **DNA Unwinding:** The DNA double helix is unwound by helicase, separating the two strands and creating a replication fork.

2. **Primer Synthesis:** RNA primase initiates lagging strand synthesis by synthesizing a short RNA primer, which provides a 3'-OH group for DNA polymerase to bind to.

3. **Okazaki Fragment Synthesis:** DNA polymerase III, with its 5' to 3' polymerase activity, elongates the RNA primer, adding new nucleotides complementary to the template strand. This results in short, discontinuous fragments of newly synthesized DNA known as Okazaki fragments.

4. **Primer Removal and Replacement:** Once an Okazaki fragment is complete, RNase H removes the RNA primer, leaving a gap. DNA polymerase I, possessing both 5' to 3' polymerase and 5' to 3' exonuclease activity, fills the gap by replacing the RNA primer with DNA nucleotides.

5. **Joining Okazaki Fragments:** DNA ligase catalyzes the formation of a phosphodiester bond between the 3'-OH end of one Okazaki fragment and the 5'-phosphate end of the adjacent fragment, linking them together to create a continuous lagging strand.

6. **Continuous Process:** As the replication fork progresses, this entire process repeats, with new RNA primers being laid down upstream, creating new Okazaki fragments, which are then processed, ligated, and added to the growing lagging strand.

Lagging strand elongation is a complex and coordinated process, involving the precise actions of multiple enzymes and proteins to ensure accurate and complete DNA replication.'
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Proteins (2)

ProteinDefinitionTaxonomy
DNA ligase 1A DNA ligase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P18858]Homo sapiens (human)
DNA polymerase alpha catalytic subunitA DNA polymerase alpha catalytic subunit that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)

Compounds (11)

CompoundDefinitionClassesRoles
digallic aciddigallic acid: structure given in first sourcebenzoate ester;
gallate ester
chloroquinechloroquine : An aminoquinoline that is quinoline which is substituted at position 4 by a [5-(diethylamino)pentan-2-yl]amino group at at position 7 by chlorine. It is used for the treatment of malaria, hepatic amoebiasis, lupus erythematosus, light-sensitive skin eruptions, and rheumatoid arthritis.

Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.
aminoquinoline;
organochlorine compound;
secondary amino compound;
tertiary amino compound
anticoronaviral agent;
antimalarial;
antirheumatic drug;
autophagy inhibitor;
dermatologic drug
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
ol-135
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