Editing Frameshift mutation (section)

==Background==

The information contained in DNA determines protein function in the cells of all organisms. Transcription and translation allow this information to be communicated into making proteins. However, an error in reading this communication can cause protein function to be incorrect and eventually cause disease even as the cell incorporates a variety of corrective measures.Genetic information is conveyed by DNA for protein synthesis within cells. Misinterpretation can lead to faulty function and disease, despite cellular correction mechanisms.

[[File:Cdmb.svg|250px|thumb|The [[central dogma]] model]]

===Central dogma===

{{Main article|Central dogma of molecular biology}}

In 1956 [[Francis Crick]] described the flow of genetic information from [[DNA]] to a specific amino acid arrangement for making a [[protein]] as the central dogma.<ref name=MBoG_6th_2008/> For a cell to properly function, proteins are required to be produced accurately for structural and for [[catalytic]] activities. An incorrectly made protein can have detrimental effects on [[Cell (biology)|cell]] viability and in most cases cause the higher [[organism]] to become unhealthy by abnormal cellular functions. To ensure that the [[genome]] successfully passes the information on, [[proofreading]] mechanisms such as [[exonuclease]]s and [[mismatch repair]] systems are incorporated in [[DNA replication]].<ref name=MBoG_6th_2008/>

===Transcription and translation===
{{Main article|Transcription (genetics)|Translation (biology)}}
[[File:Translation-genetics.png|200px|thumb|The [[Translation (biology)|translation]] process]]
After DNA replication, the reading of a selected section of genetic information is accomplished by [[transcription (genetics)|transcription]].<ref name=MBoG_6th_2008/>
Nucleotides containing the genetic information are now on a single strand messenger template called [[mRNA]]. The mRNA is incorporated with a subunit of the [[ribosome]] and interacts with an [[rRNA]]. The genetic information carried in the codons of the mRNA are now read (decoded) by anticodons of the tRNA. As each codon (triplet) is read, [[amino acids]] are being joined until a [[stop codon]] (UAG, UGA or UAA) is reached. At this point the [[polypeptide]] (protein) has been synthesised and is released.<ref name=MBoG_6th_2008/> For every 1000 amino acid incorporated into the protein, no more than one is incorrect. This fidelity of codon recognition, maintaining the importance of the proper reading frame, is accomplished by proper base pairing at the ribosome A site, [[Guanosine triphosphate|GTP]] hydrolysis activity of [[EF-Tu]] a form of kinetic stability, and a proofreading mechanism as EF-Tu is released.<ref name=MBoG_6th_2008/>

Frameshifting may also occur during [[prophase]] translation, producing different proteins from overlapping open reading frames, such as the gag-pol-env [[retroviral]] proteins. This is fairly common in [[viruses]] and also occurs in [[bacteria]] and [[yeast]] (Farabaugh, 1996). [[Reverse transcriptase]], as opposed to [[RNA Polymerase II]], is thought to be a stronger cause of the occurrence of frameshift mutations. In experiments only 3–13% of all frameshift mutations occurred because of RNA Polymerase II. In [[prokaryotes]] the error rate inducing frameshift mutations is only somewhere in the range of .0001 and .00001.<ref name="rna polymerase II">{{cite journal|last=Zhang|first=J|title=Host RNA polymerase II makes minimal contributions to retroviral frame-shift mutations.|journal=The Journal of General Virology|date=August 2004|volume=85|issue=Pt 8|pages=2389–95|pmid=15269381 |doi=10.1099/vir.0.80081-0|doi-access=free}}</ref>

There are several biological processes that help to prevent frameshift mutations. Reverse mutations occur which change the mutated sequence back to the original [[wild type]] sequence. Another possibility for mutation correction is the use of a [[suppressor mutation]]. This offsets the effect of the original mutation by creating a secondary mutation, shifting the sequence to allow for the correct amino acids to be read. [[Guide RNA]] can also be used to insert or delete Uridine into the mRNA after transcription, this allows for the correct reading frame.<ref name=MBoG_6th_2008/>

===Codon-triplet importance===

{{Main article|Genetic code}}

[[File:RNA-codons-aminoacids.svg|300px|thumb|The three letter code, the [[codon]]]]
A [[codon]] is a set of three [[nucleotides]], a triplet that codes for a certain [[amino acid]]. The first codon establishes the reading frame, whereby a new codon begins. A protein's amino acid backbone [[sequence]] is defined by contiguous triplets.<ref name=Cox08>{{cite book |last1=Cox |first1=Michael |last2=Nelson |first2=David R. |last3=Lehninger |first3=Albert L |title=Lehninger principles of biochemistry |publisher=W.H. Freeman |location=San Francisco |year=2008 |isbn=978-0-7167-7108-1 |url-access=registration |url=https://archive.org/details/lehningerprincip00lehn_1 }}</ref> Codons are key to translation of genetic information for the synthesis of proteins. The reading frame is set when translating the mRNA begins and is maintained as it reads one triplet to the next. The reading of the genetic code is subject to three rules the monitor codons in mRNA. First, codons are read in a 5' to 3' direction. Second, codons are nonoverlapping and the message has no gaps. The last rule, as stated above, that the message is translated in a fixed reading frame.<ref name=MBoG_6th_2008/>
[[File:Point Mutation.jpg|250px|thumb|Example of different types of point mutations]]
<!-- Deleted image removed: [[File:Frameshift mutations.jpg|250px|thumb|Example of amino acid changes in frameshift mutation]] -->