The Termination is the final phase in DNA replication. It is preceded by initiation and elongation. An early termination of the replication can result in the expression of shortened proteins and thus a mutation.
Termination is the final phase in DNA replication.
During replication or reduplication, the genetic information carrier DNA is multiplied in individual cells. The duplication takes place according to the semi-conservative principle and usually leads to an exact duplication of the genetic information. Replication is triggered during the synthesis phase, before the mitosis phase, and thus takes place before the cell nucleus divides.
At the beginning of the replication, the DNA double strand is separated into single strands, on which new complementary strands are formed. Each DNA strand is determined by the base sequence of the opposite strand. DNA replication occurs in several phases. Termination is the third and therefore final phase of replication. The termination is preceded by initiation and elongation.
A synonymous term for the expression of termination in this context is the designation Termination phase. Termination here means "abort" or "termination". During the termination, the newly formed mRNA strand becomes detached from the actual DNA. The work of DNA polymerase is slowly coming to an end. The termination of DNA replication should not be confused with the termination of replication of RNA.
In the replication phase of initiation, primarily the regulation of replication takes place. The starting point of the replication is determined and so-called priming takes place. After the initiation, the polymerization begins, during which the elongation phase is passed through. The enzyme DNA polymerase separates complementary strands of the DNA into single strands and reads the bases of the single strands one after the other. In this phase semi-discontinuous doubling takes place, which includes another phase of priming.
Only after initiation and elongation does the termination phase follow within replication. The termination differs from life form to life form. In eukaryotes like humans, the DNA is structured in a ring. It also includes termination sequences that correspond to two different sequences, each of which is relevant for a replication fork.
The termination is usually not triggered by special mechanisms. As soon as two replication forks run together or the DNA ends, the replication is automatically ended at this point. The replication is terminated in an automatic mechanism.
Termination sequences are control elements. They ensure that the replication phase arrives at a specific end point in a controlled manner despite the different replication speeds in the two replication forks. All termination sites correspond to binding sites for the Tus protein, the "terminus utilizing substance". This protein blocks the replicative helicase DnaB and thus stops replication.
In eukaryotes, the replicated ring strands remain connected to one another even after replication. The connection corresponds to the terminal point. Only after cell division are they separated by various processes and can thus be divided. The connection that remains until after cell division appears to play a role in the controlled distribution.
There are two main mechanisms that play a role in the final separation of the DNA rings. Enzymes such as type I and type II topoisomerase are involved in the separation. Finally, an auxiliary protein recognizes the stop codon during termination. This causes the polypeptide to fall off the ribosome, since no t-RNA with a suitable anticodon for the stop codon is available. Ultimately, the ribosome breaks down into its two subunits.
All processes for the duplication of the genetic material in the sense of replication are complicated and require a high expenditure of substances and energy within the cell. For this reason, spontaneous replication errors can easily occur. If the genetic material changes spontaneously or induced from outside, we speak of mutations.
Replication errors can lead to missing bases, be associated with changed bases, or be due to incorrect base pairing. In addition, deletion and insertion of single or multiple nucleotides within the two DNA strands can lead to replication errors. The same applies to pyrimidine dimers, strand breaks and cross-linking errors in the DNA strands.
Separate repair mechanisms are available in the event of a replication error. Many of the errors mentioned are corrected as far as possible by DNA polymerase. The replication accuracy is relatively high. The error rate is only one error per nucleotide, which is due to different control systems.
For example, a control mechanism of eukaryotic cells is known as nonsense-mediated mRNA decay, which can recognize undesired stop codons within the mRNA and thus prevent shortened proteins from finding expression.
Premature stop codons in the mRNA are due to gene mutations. So-called nonsense mutations or alternative and faulty splicing can result in shortened proteins that are affected by functional losses. The control mechanisms cannot always correct the errors.
There are three different forms of the autosomal recessive inherited disorder β-thalassemia: the first is homozygous thalassemia, a serious illness that can be traced back to your nonsense mutation. Heterozygous thalassemia is a milder disease in which the nonsense mutations are only found in a single copy of the β-globin gene. Through the mechanism of nonsense-mediated mRNA decay, the mRNA of the faulty gene can be degraded to such an extent that only healthy genes are expressed.
In heterozygous thalassemia and thus the moderate form of the disease, the nonsense mutation is in the last mRNA exon, so that the control mechanisms are not activated. For this reason, in addition to healthy β-globin, shortened β-globin is also formed.Erythrocytes with the defective β-globin perish.
Another example of the failure of the control mechanism is Duchenne muscular dystrophy, which is also due to a nonsense mutation in the mRNA. In this case, the control mechanism breaks down the mRNA, but thus causes a total loss of the so-called dystrophin protein.