Chapter 7.2: Molecular Mechanisms of Mutation Flashcards
Describe irradiation mutation
o Irradiation causes the formation of free radicals that can alter individual bases
Descibe microhomology-mediated end-joining (MMEJ)
• Deals with double-strand breaks that haven’t been connected by homologous recombination or NHEJ • Similar to NHEJ except in MMEJ, the broken DNA ends are cut back on either side of the break (resected) by enzymes • The resection exposes small single-stranded regions of complementary DNA sequence (“microhomology”) on either side of the break that help in bringing the ends together • Typically results in small deletions
Describe how UV radiation form dimers
o Ultraviolet (UV) radiation causes adjacent Ts to form dimers (thymine-thymine dimers), which can disrupt the readout of genetic information
Describe SOS system (bacteria) repair
SOS system (bacteria) relies on error-prone DNA polymerases • Produced only in the presence of DNA damage
Describe X-ray deletion
o X-rays break the sugar-phosphate backbone and thereby split a DNA molecule into smaller pieces, which may be ligated back together improperly
Define mutagen
o Any physical or chemical agent that raises the frequency of mutations above the spontaneous rate
Describe repair of double-strand breaks by nonhomologous end-joining (NHEJ)
Important for the repair of double-strand breaks formed during the G1 phase of the cell cycle Proteins participating in NHEJ bind to DNA ends at the site of the breakage and protect the ends from nucleases The NHEJ proteins also bridge the two ends, allowing them to be stitched together by DNA ligase enzyme
What is o Any physical or chemical agent that raises the frequency of mutations above the spontaneous rate?
mutagen
How do intercalators contribute to mutations?
o Intercalators: flat, planar molecules that can sandwich themselves between successive base pairs and disrupt the machinery for replication, generating deletions or insertions of a single base pairing
Describe deamination
o In deamination, the removal of an amino group from C initiates a process that causes a transition after DNA replication
How do base analogs contribute to mutations?
o Base analogs are so similar in chemical structure to the normal nitrogenous bases that the replication machinery can incorporate them into DNA (base substitutions)
What are pre-mutation alleles?
Because larger repeat numbers mean more instability, some alleles with intermediate numbers of trinucleotide repeats behave as so-called pre-mutation alleles
Describe nucleotide excision repair
o Nucleotide excision repair removes alteration that base excision cannot repair because the cell lacks a DNA glycosylase that recognizes the problem base
Describe methyl-directed mismatch repair
Describe slipped mispairings
Describe the Ames Test
Describe the proofreading function of DNA polymerase
Nuclease portion of the polymerase molecule, called the 3’-to-5’ exonuclease, recognizes a mispaired base and excises it, allowing the polymerase to copy the nucleotide correctly on the next try
Describe depuriniation
o In depurination, the hydrolysis of A or G bases leaves a DNA strand with an unspecified base
Describe base excision repair
Enzymes called DNA glycosylases clave an altered nitrogenous base from the sugar of its nucleotide, releasing the base and creating an apurinic or apyrimidinic (AP) site in the DNA chain
Describe base tautomerization
Each of the four bases has two tautomers, similar chemical forms that interconvert continually Rare tautomeric forms of bases have altered bases pairing ability Tautomerization causes single base pair mutations
What is the Ames test used for?
o The US FDA tries to identify carcinogens by using the Ames test to screen for chemicals that cause mutations in bacterial cells
How do trinucleotide repeats expand and contract?
slipped mispairing
