What Kind of Mutation Occurs When One Base Is Changed to Another at a Single Location in the Dna?

DNA Mutation and Repair

A mutation, which may arise during replication and/or recombination, is a permanent change in the nucleotide sequence of DNA. Damaged DNA can be mutated either by substitution, deletion or insertion of base pairs. Mutations, for the about role, are harmless except when they lead to cell expiry or tumor germination. Because of the lethal potential of Deoxyribonucleic acid mutations cells have evolved mechanisms for repairing damaged Deoxyribonucleic acid.

Types of Mutations

In that location are three types of Dna Mutations: base of operations substitutions, deletions and insertions.

1. Base Substitutions

Single base substitutions are called point mutations, recall the indicate mutation Glu -----> Val which causes sickle-cell disease. Point mutations are the most common type of mutation and there are 2 types.

Transition: this occurs when a purine is substituted with another purine or when a pyrimidine is substituted with another pyrimidine.

Transversion: when a purine is substituted for a pyrimidine or a pyrimidine replaces a purine.

Signal mutations that occur in DNA sequences encoding proteins are either silent, missense or nonsense.

Silent: If abase substitution occurs in the third position of the codon there is a good chance that a synonymous codon will be generated. Thus the amino acid sequence encoded past the cistron is non inverse and the mutation is said to exist silent.

Missence: When base exchange results in the generation of a codon that specifies a dissimilar amino acrid and hence leads to a dissimilar polypeptide sequence. Depending on the blazon of amino acid substitution the missense mutation is either bourgeois or nonconservative. For example if the structure and backdrop of the substituted amino acid are very like to the original amino acid the mutation is said to exist conservative and will most probable accept trivial outcome on the resultant proteins structure / office. If the exchange leads to an amino acid with very different construction and properties the mutation is nonconservative and will probably be deleterious (bad) for the resultant proteins structure / function (i.east. the sickle jail cell point mutation).

Nonsense: When a base exchange results in a end codon ultimately truncating translation and most likely leading to a nonfunctional protein.

2. Deletions

A deletion, resulting in a frameshift, results when one or more base pairs are lost from the DNA (meet Figure in a higher place). If one or 2 bases are deleted the translational frame is altered resulting in a garbled message and nonfunctional product. A deletion of three or more bases leave the reading frame intact. A deletion of one or more codons results in a poly peptide missing one or more amino acids. This may be deleterious or not.

3. Insertions

The insertion of additional base pairs may lead to frameshifts depending on whether or not multiples of iii base pairs are inserted. Combinations of insertions and deletions leading to a variety of outcomes are also possible.

Causes of Mutations

Errors in Deoxyribonucleic acid Replication

On very, very rare occasions Dna polymerase will incorporate a noncomplementary base into the daughter strand. During the next round of replication the missincorporated base would lead to a mutation. This, however, is very rare as the exonuclease functions as a proofreading mechanism recognizing mismatched base pairs and excising them.

Errors in Deoxyribonucleic acid Recombination

Dna frequently rearranges itself by a procedure called recombination which gain via a variety of mechanisms. Occasionally DNA is lost during replication leading to a mutation.

Chemical Harm to Deoxyribonucleic acid

Many chemical mutagens, some exogenous, some man-made, some environmental, are capable of damaging Deoxyribonucleic acid. Many chemotherapeutic drugs and intercalating agent drugs function by damaging DNA.

Radiation

Gamma rays, X-rays, even UV light tin can interact with compounds in the cell generating costless radicals which cause chemical impairment to DNA.

Dna Repair

Damaged DNA tin can be repaired by several different mechanisms.

Mismatch Repair

Sometimes Dna polymerase incorporates an incorrect nucleotide during strand synthesis and the 3' to 5' editing organisation, exonuclease, fails to correct it. These mismatches as well as single base insertions and deletions are repaired by the mismatch repair mechanism. Mismatch repair relies on a secondary bespeak within the Deoxyribonucleic acid to distinguish between the parental strand and daughter strand, which contains the replication error. Human cells posses a mismatch repair system like to that of Eastward. coli, which is described hither. Methylation of the sequence GATC occurs on both strands sometime later on Dna replication. Because Deoxyribonucleic acid replication is semi-conservative, the new daughter strand remains unmethylated for a very short menstruum of time following replication. This difference allows the mismatch repair system to determine which strand contains the fault. A protein, MutS recognizes and binds the mismatched base pair.

Another protein, MutL then binds to MutS and the partially methylated GATC sequence is recognized and bound by the endonuclease, MutH. The MutL/MutS circuitous and so links with MutH which cuts the unmethylated Dna strand at the GATC site. A DNA Helicase, MutU unwinds the Deoxyribonucleic acid strand in the direction of the mismatch and an exonuclease degrades the strand. Dna polymerase and then fills in the gap and ligase seals the nick. Defects in the mismatch repair genes establish in humans appear to exist associated with the development of hereditary colorectal cancer.

Nucleotide Excision Repair (NER)

NER in human cells begins with the formation of a complex of proteins XPA, XPF, ERCC1, HSSB at the lesion on the Deoxyribonucleic acid. The transcription factor TFIIH, which contains several proteins, and then binds to the circuitous in an ATP dependent reaction and makes an incision. The resulting 29 nucleotide segment of damaged Dna is then unwound, the gap is filled (Dna polymerase) and the nick sealed (ligase).

Direct Repair of Damaged DNA

Sometimes impairment to a base can exist directly repaired by specialized enzymes without having to excise the nucleotide.

Recombination Repair

This mechanism enables a jail cell to replicate past the damage and prepare information technology afterwards.

Regulation of Harm Control

DNA repair is regulated in mammalian cells by a sensing mechanism that detects DNA damage and activates a poly peptide called p53. p53 is a transcriptional regulatory factor that controls the expression of some cistron products that touch cell cycling, DNA replication and Deoxyribonucleic acid repair. Some of the functions of p53, which are only existence determined, are: stimulation of the expression of genes encoding p21 and Gaad45. Loss of p53 function tin can exist deleterious, about 50% of all human cancers have a mutated p53 gene.

The p21 poly peptide binds and inactivates a cell sectionalisation kinase (CDK) which results in jail cell bike arrest. p21 too binds and inactivates PCNA resulting in the inactivation of replication forks. The PCNA/Gaad45 circuitous participates in excision repair of damaged DNA.

Some examples of the diseases resulting from defects in Deoxyribonucleic acid repair mechanisms.

Xeroderma pigmentosum

Cockayne's syndrome

Hereditary nonpolyposis colorectal cancer

© Dr. Noel Sturm 2019

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Source: http://www2.csudh.edu/nsturm/CHEMXL153/DNAMutationRepair.htm

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