types of chemical mutagens
- deaminating agents
- alkylating agents
- intercalating agents
A certain amount of base __ occurs spontaneously in genomic DNA molecules.
- deamination (removal of an amino group)
Rate of deamination is increased by some compounds such as __
- nitrous acid (deaminates adenine, cytosine, and guanine)
- sodium bisulfite (acts only on cytosine)
Guanine deaminates into __
xanthine, which blocks replication (not mutagenic)
Adenine deaminates into __
hypoxanthine (pairs with C)
Cytosine deaminates into __
uracil (pairs with A)
Deamination of __ results in point mutations when __
A & C; the template strand is copied
(since hypoxanthine pairs with C & uracil pairs with A)
Which base cannot deaminate?
thymine (because there is no amine group)
__ agents give rise to point mutations
Alkylating (by adding methyl and ethyl)
Compounds such as Ethylmethane sulfonate (EMS) & methylating agents (such as methyl halides) are methylations that often result in __
modified nucleotides with altered base pairing properties that lead to point mutations
Some alkylations block replication by forming __, or the added __ groups prevent progress of the replication complex.
- cross-links between the 2 strands of DNA;
- large alkyl
__ agents are usually associated with insertion or deletion mutations
Ethidium bromide and other intercalating agents are flat molecules that can __
slip between base pairs in the double helix, slightly unwinding the helix & hence, increasing the distance between adjacent base pairs (can affect the # of bases)
types of physical mutagens
- UV radiation
- ionizing radiation
UV radiation of wavelength 260nm induces __ of adjacent pyrimidine bases especially if these are both __ resulting in a __
dimerization; thymines; cyclobutyl dimer
(Other pyrimidine combos also form dimers - order of frequency: 5'-CT-3', 5'-TC-3', 5'-CC-3')
UV-induced dimerization results in __
DNA polymerase stalling when it reaches the dimers. A deletion mutation occurs when the modified strand is copied.
A type of UV-induced base dimer is the photoproduct (6-4) lesion, in which __
carbons number 4 & 6 of adjacent pyrimidines become covalently linked
UV-induced base dimer (photo)
Ionization radiation may cause __
- point mutations
- insertion and/or deletion
- double strand break
Severe forms of DNA damage blocks the subsequent replication of the genome.
Some types of ionization radiation act directly on DNA, other act indirectly by stimulating __
the formation of reactive molecules such as peroxides in the cell
Oxidation of guanine results in __
Guanine turning into oxoG, which pairs with C and also with A.
Base pairing with A → transversion
agents that cause double strand break
examples: ionizing radiation and drugs such as bleomycin
Heat enhances the water-induced __. This occurs more frequently with purines than with pyrimidines and results in an __
- cleavage/hydrolysis of the b-N-glycosidic bond that attaches the base to the sugar component of the nucleotide;
- AP (apurinic/apyrimidinic) site, or baseless site
the effect of heat-induced hydrolysis on double-stranded DNA
- The sugar-phosphate is left unstable and rapidly degrades, leaving a gap
Is heat-induced hydrolysis normally mutagenic?
no. Since the DNA molecule is double stranded, cells have effective systems for repairing gaps.
- has no effect on the coding function. e.g. causing no change in the coded amino acids or level of expression of a gene
- occur in intergenic DNA and in the noncoding components of genes and gene related sequences
In other words, some 98.5% of the human genome can be mutated without a significant effect.
- The new codon specifies the same amino acid as the unmutated codon (is a form of silent mutation)
- The mutation alters the codon so that is specifies a different amino acid (missense mutation)
- The mutation may convert a codon that specifies an amino acid into a termination codon. It usually has a drastic effect on the function.
read through mutation
- The mutation converts a termination codon into a codon specifying an amino acid, resulting in protein extension