Termination is the final phase in DNA replication. It is preceded by initiation and elongation. Premature termination of replication can result in the expression of truncated proteins and thus mutation.
What is termination?
Termination is the final stage in DNA replication. During replication or reduplication, the genetic information carrier DNA is multiplied in individual cells. Replication occurs according to semiconservative principles and usually results in an exact duplication of the genetic information. Replication is initiated during the synthesis phase, before the phase of mitosis, and thus takes place before cell nucleus division. The DNA double strand is separated into single strands at the beginning of replication, where new formation of complementary strands occurs. Each DNA strand is determined by the base sequence of the opposite strand. DNA replication occurs in several phases. Termination is the third and final phase of replication. Termination is preceded by initiation and elongation. A synonymous term for the expression of termination in this context is the term termination phase. Termination stands here in the meaning of “termination” or “termination”. During termination, the newly formed mRNA partial strand detaches from the actual DNA. The work of the DNA polymerase thus slowly comes to an end. Termination of DNA replication should not be confused with replication termination of RNA.
Function and task
The replication phase of initiation is primarily where the regulation of replication takes place. The starting point of replication is determined and the so-called priming takes place. After initiation, polymerization begins, in which the elongation phase is passed through. The enzyme DNA polymerase separates complementary strands of DNA into single strands and reads the bases of the single strands one after the other. Semidiscontinuous duplication takes place in this phase, which includes a repeated phase of priming. Only initiation and elongation are followed within replication by the phase of termination. Termination differs from life form to life form. In eukaryotes such as humans, DNA has a circular structure. It includes termination sequences corresponding to two distinct sequences, each of which is relevant to a replication fork. Termination is not usually triggered by special mechanisms. As soon as two replication forks run into each other or the DNA terminates, replication is automatically terminated at this point. Thus, termination of replication occurs in an automatism. Termination sequences are control elements. They ensure that the phase of replication reaches a specific end point in a controlled manner despite different replication rates in the two replication forks. All termination sites correspond to binding sites for the Tus protein, the “terminus utilizing substance”. This protein induces a blockade of the replicative helicase DnaB, initiating the arrest of replication. In eukaryotes, replicated ring strands remain connected after replication. The connection corresponds to each of the terminal sites. Only after cell division are they separated by various processes, allowing them to split. The persistent connection until after cell division seems to play a role in controlled distribution. Two main mechanisms play a role in the final separation of 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. Thus, the polypeptide falls off the ribosome because no t-RNA with a suitable anticodon for the stop codon is available. Thus, the ribosome ultimately breaks down into its two subunits.
Diseases and disorders
All of the processes involved in duplicating the genetic material in terms of replication are complicated and require a great deal of materials and energy within the cell. Spontaneous errors in replication can easily occur for this reason. When spontaneously, or externally induced, the genetic material changes, we talk about mutations. Replication errors can result in missing bases, be associated with altered bases, or be due to incorrect base pairing.In addition, deletion and insertion of single or multiple nucleotides within the two DNA strands can also lead to replication errors. The same applies to pyrimidine dimers, strand breaks and cross-linking errors of the DNA strands. Intrinsic repair mechanisms are available in the event of a replication error. Thus, 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 various control systems. Nonsense-mediated mRNA decay, for example, is a control mechanism of eukaryotic cells that can detect unwanted stop codons within the mRNA and thus prevent truncated proteins from finding expression. Premature stop codons in mRNA result from gene mutations. So-called nonsense mutations or alternative and defective splicing can give rise to truncated proteins that are affected by loss of function. Control mechanisms cannot always correct the errors. There are three different forms of the autosomal recessive disease β-thalassemia: the first is homozygous thalassemia, a severe disease resulting from your nonsense mutation. Heterozygous thalassemia is a milder disease in which the nonsense mutations are only in a single copy of the β-globin gene. Through the mechanism of nonsense-mediated mRNA decay, the mRNA of the defective gene can be degraded to the extent that only healthy genes are expressed. In heterozygous thalassemia, and thus the moderately severe form of the disease, the nonsense mutation is located in the last mRNA exon, so that the control mechanisms are not activated. For this reason, truncated β-globin is produced in addition to healthy β-globin. 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 degrades the mRNA but thus causes a total loss of the so-called dystrophin protein.
