ch 16 genetics terms
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refers to the alteration of a single base pair of DNA or of a small number of adjacent base pairs
replacement of a base by the other base of the same chemical category; ex A to G or G to A and C to T or T to C
replacement of a base of one chemical category by a base of the other; ex purine (A or G) replaced by pyrimidine (C or T)
the mutation changes one codon for an amino acid into another codon for that same amino acid. AKA silent mutations
missense mutation (conservative)
The codon for one amino acid is changed into a codon for another amino acid, but the altered amino acide is chemcially similar
missense mutation (nonconservative)
The codon for one amino acid is changed into a codon for another amino acid, and the amino acid is chemically dissimilar
Altered codon signals chain termination, i.e. STOP codon
insertion or deletion of a single base pair of DNA which changes the reading frame for the translation process, causing the entire amino acid sequence downstream of the mutant site to bear no relation to the original amino acid sequence. Typically result in complete loss of normal protein structure and function
isomers that differ in the positions of their atoms and in the bonds between the atoms; each of the bases in DNA can appear in one of several forms, called tautomers
form of each base that is normally present in DNA
naturally occurring damage to the DNA that can generate mutations
the more commone form of spontaneous lesion. The loss of a purine base.
deamination of cytosine yields uracil when H2O is transitioned into NH3
a mechanism of spontaneous lesion that is a side effect of aerobic metabolism. The active oxygen species can cause damage to DNA as well as to DNA precursors, resulting in mutation.
production of mutations in the lab through exposure to mutagens
some chemical compounds are sufficiently similar to the normal nitrogen base of DNA that they occasionally are incorporated into DNA in place of normal bases. They are incorporated into DNA during DNA synthesis. They have pairing properties unlike the normal bases, thus they can produce mutations by causing incorrect nucleotides to be inserted during replication.
three mechanisms of mutagenesis
replace a base; alter a base to mispair; damage a base so no pairing can occur
forms of base damage
- UV light: generates alteration in DNA called photoproducts
- Ionizing radiation: formation of ionized and excited molecules that can damage DNA, or more commonly, cause breakage of bonds
- chemical carcinogens: bulky addition products cause breakage between base and the sugar
planar molecules that mimic base pairs and are able to slip themselves in between the stacked nitrogen bases at the core of the DNA double helix. In this position, it can cause insertion or deletion of a nucleotide pair
direct reversal of damaged DNA as a biological repair mechanism
The most straightforward way to repair a lesion is to reverse it directlly, regenerating the normal base. Most damages are irreversible, but some can be fixed. Alkyltransferases remove alkyl group, and photolyases split pyrimidine dimers
homology dependent rapair systems
repair using sequence complementarity to replace damaged bases.
damaged bases are removed and repaird through sequential action of DNA glycosylase(cleave base-sguar bonds), AP endonuclease (cuts damaged strand upstream), dRpase (cleans up backbone), DNA polymerase (refills backbone gap with nucleotides), and ligase (seals new nucleotide into backbone)
nucleotide-excision repair (NER)
repairs bulky damage; activated when global genomic repair (GGR) recognizes nontranscribed regions, or when Transcritpion-coupled NER (TC-NER) finds transcribed regions of the genome. A multiprotein complex then excises several bases and resynthesizes them using the opposite strand as a template
- - conserved from bacteria to humans
- - corrects replication errors in newly synthesized DNA
- -100fold decrease in replication errors
- Mismatch repair system have to do at least three things:
- 1) recognize mismatched BP 2) determine which base is incorrect 3) excise the incorrect base and carry out repair synthesis
accommodate damaged bases; in general have a higher error rate; dissociate after adding a few nucleotides
nonhomologous end joining (NHEJ)
One method used to put double standed broken ends back together. Error-prone. 1) recognize damage 2) KU70 and KU80 bind to broken ends, forming heterodimer 3) ligase joins the two ends.
synthesis-dependent strand annealing (SDSA)
error-free repair mechanism that can correct damage if the break in the double strand occurs after replication of a chromosomal region in a dividing cell. It uses sister chromatids available in mitosis as the templates to ensure a correct repair
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