Chapter 19: Gene Mutation, DNA Repair, and Recombination

mutation

a permanent change in the genetic material that can be passed from cell to cell or, if it occurs in reproductive cells, from parent to offspring

allelic

mutations provide _____ variation

evolutionary, adapt

mutations are the foundation for _____ change

* provide the variation that enables species to _____ to their environment via natural selection

harmful, diseases

new mutations can be _____ to the individual and often are the cause of _____

chromosome mutation

big changes in chromosome structure

genome mutation

changes in chromosome number

gene mutation

relatively small changes in DNA structure that affects a single gene

point mutations

a change in a single base pair within DNA

base substitution

a point mutation in which one base is substituted for another

transition

a point mutation involving a change of a pyrimidine to another pyrimidine (ex. C to T) or a purine to another purine (ex. A to G)

transversion

a point mutation in which a purine is interchanged with a pyrimidine, or vice versa

silent mutation

a mutation that does not alter the amino acid sequence of the encoded polypeptide even though the base sequence has changed

degenerate, third

because the genetic code is _____, silent mutations can occur in certain bases within a codon, such as the _____ base, and the specific amino acid is not changed

missense mutation

a base substitution that leads to a change in the amino acid sequence of the encoded polypeptide

nonsense mutation

a mutation that involves a change from a normal codon to a stop codon. This change terminates the translation of the polypeptide earlier than normal, producing a truncated polypeptide.

frameshift mutation

a mutation that involves the addition or deletion of a number of nucleotides not divisible by 3. Because the codons are read in multiples of 3, this type of mutation shifts the reading frame. The translation of the mRNA then results in a completely different amino acid sequence downstream from the mutation.

reduced, enhanced

except for silent mutations, new mutations are more likely to produce polypeptides that have _____ rather than _____ function

neutral mutation

a missense mutation that has no detectable effect on protein function or no detectable effect on the survival of the organism

neutral

a missense mutation that substitutes an amino acid with a chemistry similar to that of the original amino acid is likely to be _____

enhanced, greater, natural selection

A mutation can occasionally produce a polypeptide with an _____ ability to function. Although such a favorable mutation is relatively rare, it may result in an organism with a _____ likelihood of surviving and reproducing. If this is the case, _____ _____ may cause the favorable mutation to increase in frequency within a population.

non-coding

a mutation can occur within a _____ sequence, thereby affecting gene expression (promoter and regulatory regions)

up promoter mutation

a mutation in a promoter that increases the rate of transcription

down promoter mutation

a mutation in a promoter that decreases the rate of transcription

wild type

a relatively prevalent genotype in a natural population

mutant allele

an allele that has been created by altering a wild-type allele by mutation

forward mutation

a mutation that changes the wild-type genotype into some new variation

reverse mutation

a mutation that changes a mutant allele back to a wild-type allele

deleterious mutation

* a mutation that is detrimental with regard to its effect on phenotype
* decreases the chances of survival and reproduction

lethal mutation

* a mutation that produces an allele that results in the death of a cell or an organism
* extreme example of a deleterious mutation

beneficial mutation

a mutation that enhances the survival or reproductive success of an organism

conditional mutant

a mutant whose phenotype depends on the environmental conditions, such as temperature-sensitive (ts) mutant

suppressor mutation

a mutation at a second site that suppresses the phenotypic effects of another mutation

intragenic, intergenic

two types of suppressor mutations

intragenic suppressor

a suppressor mutation that is within the same gene as the first mutation that it suppresses

inhibits, same, restores

intragenic suppressor:

* mutation 1: _____ protein function
* mutation 2: occurs in _____ protein and _____ protein function

intergenic suppressor

a suppressor mutation that occurs in a different gene than the gene that contains the first mutation

inhibits, another

intergenic suppressor:

* mutation 1: _____ protein function
* mutation 2: alters _____ protein to perform that function

inhibits, different

redundant function (intergenic suppressor):

* a first mutation _____ the function of a protein, and a second mutation alters a _____ protein to carry out that function

defect, increases

common pathway (intergenic suppressor):

* two or more different proteins may function as enzymes in a common pathway
* a mutation that causes a _____ in one enzyme may be compensated for by a mutation that _____ the function of a different enzyme in the same pathway

inhibits, suppressed

multimeric protein (intergenic suppressor):

* a mutation in a gene encoding one protein subunit that _____ function may be _____ by a mutation in a gene that encodes a different subunit

loss, activate

transcription factor (intergenic suppressor):

* a first mutation causes _____ of function of a particular protein
* a second mutation may alter a transcription factor and cause it to _____ the expression of another gene
* this other gene encodes a protein than can compensate for the loss of function causes by the first mutation

breakpoint

a region where two chromosome pieces break apart and rejoin with other chromosome pieces

position effect

a change in phenotype that occurs when the location of a gene changes from one chromosomal site to a different one

inversion

* type of position effect
* a gene may be moved next to regulatory sequences for a different gene, such as silencers or enhancers, and those then influence the expression of the relocated gene

translocation

* type of position effect
* a chromosomal rearrangement may reposition a gene from a less condensed, or euchromatic region of the chromosome, where it is active, to a very highly condensed, or heterochromatic region of a chromosome, where its expression may be turned off

germ-line and somatic

two types of animal cells

germ-line

refers to cells that give rise to gametes

germ-line mutation

a mutation in a sperm or egg cell, or in a precursor cell that produces the gametes

entire, half, can

germ-line mutation → mutation is found throughout the _____ body → _____ of the gametes carry the mutation → _____ be passed down

somatic cell

any cell of the body except for gametes and germ-line cells that give rise to gametes

somatic mutation

a mutation in a somatic cell

portion, none, cannot

somatic mutation → _____ of the body contains the mutation → _____ of the gametes carry the mutation → _____ be passed down

spontaneous mutation

a change in DNA structure that results from natural biological or chemical processes

depurination

* type of spontaneous mutation
* the removal of a purine base (adenine or guanine) from DNA

purine, covalent, unstable, apurinic, 75%

depurination:

* the removal of a _____ base from DNA
* the _____ bond between deoxyribose and a purine base is somewhat _____ and occasionally undergoes a spontaneous reaction with water that releases the base from the sugar, thereby creating an _____ site
* replication across from AP site has a _____ chance of being a mutation during DNA replication
* becomes a mutation if repair system fails to fix the apurinic site and during DNA replication

apurinic site

a site in DNA that is missing a purine base

any

resulting mutation of depurination:

* because a complementary base is not present to specify the incoming base for the new strand at the apurinic site, _____ of the four bases are added to the new strand in the region that is opposite the apurinic site

deamination

* type of spontaneous mutation
* the removal of an amino group from a cytosine base to produce uracil

amino, cytosine, uracil, adenine, guanine

deamination:

* the removal of an _____ group from the _____ base to produce _____
* if repairing does not take place, a mutation may result because uracil hydrogen bonds with adenine during DNA replication
* if a DNA template strand has uracil instead of cytosine, a newly made strand will incorporate _____ instead of _____

adenine, guanine

resulting mutation of deamination:

* if a DNA template strand has uracil instead of cytosine, a newly made strand will incorporate _____ instead of _____

tautomeric shift

* type of spontaneous mutation
* a temporary change in chemical structure, such as an alternation between the keto and enol forms of the bases that are found in DNA

tautomers

chemically similar forms of certain small molecules, such as bases, which can spontaneously interconvert

temporary, keto, enol, amino, imino, keto, amino, TG, CA

tautomeric shift:

* _____ change in base structure


* G and T: _____ & _____
* A and C: _____ & _____
* common, stable form of G and T: _____
* common, stable form of A and C: _____
* the presence of enol and imino can cause a mutation because these rare forms do not conform to the AT/GC rule of base pairing
* instead, if one of the bases is in the enol or imino form, hydrogen bonding will promote _____ and _____ base pairs
* mutation if shift occurs during DNA replication

AC/GT

resulting mutation of tautomeric shift:

* _____ base pairing instead of AT/GC base pairing

oxidative damage

* type of spontaneous mutation
* changes in DNA structure that are caused by reactive oxygen species ROS

hydrogen peroxide, superoxide, and hydroxyl radical

examples of reactive oxygen species (ROS)

8-oxoguanine, 8-oxoguanine, transversion

oxidative damage:

* guanine → _____
* _____ base-pairs with adenine, not cytosine, during DNA replication (_____: purine to pyrimidine)

adenine, cytosine

resulting mutation of oxidative damage:

* 8-oxoguanine base-pairs with _____, not _____, during DNA replication, causing mutations in which a GC base pair becomes a TA base pair

trinucleotide repeat expansion (TNRE)

a type of mutation that involves an increase in the number of tenderly repeated trinucleotide sequences

increase, symptoms, CAG, glutamine, glutamine, longer, stronger

trinucleotide repeat expansion (TNRE):

* a type of mutation that involves an _____ in the number of tenderly repeated trinucleotide sequences
* the length of a trinucleotide repeat has increased above a critical size → causes disease _____
* commonly _____ repeats
* encodes _____
* long tracts of _____ → causes proteins to aggregate
* each generation can have _____ tracks and _____ symptoms

hairpin, increase, gamete, longer

How does TRNE occur?

* _____ formation (formation of CG base pairs)
* causes _____ in length of repeat during replication
* when the trinucleotide repeat sequence is abnormally long, such expansions may frequently occur during _____ formation, and therefore offspring in successive generations may have trinucleotide repeat sequence that are even _____ than those in their parents

induced mutation

a change in DNA structure causes by an environmental agent

chemical, physical

environmental agents of induced mutations can be either _____ or _____

base modifier, intercalating agent, base analogue

chemical mutagens (induced mutation)

ionizing radiation, nonionizing radiation

physical mutagens (induced mutation)

mutagen

an agent that can alter the structure of DNA, causing a mutation

deamination, amino, keto, NH2, O, uracil, adenine, hypoxanthine, cytosine, nitrogen mustard, ethyl methanesulfonate (EMS)

base modification:

* covalently modifies the structure of bases
* _____
* nitrous acid replaces _____ groups with _____ groups
* _____ to _____
* deamination changes cytosine to _____ → binds to _____ instead of guanine
* deamination changes adenine to _____ → binds to _____ instead if thymine
* examples of alkylating agents: _____ (2 words) and _____ (2 words)

ethidium bromide, acridine dyes, frameshift

intercalating agents:

* directly interferes with the DNA replication process
* _____ _____ and _____ _____ contain flat structures that insert themselves between adjacent base pairs, thereby distorting the helical structure
* when DNA containing these mutagens is replicated, single-nucleotide additions and/or deletions can occur in the newly made daughter strands, creating _____ mutations

5-bromouracil, keto, enol

base analogues:

* _____: thymine analog that can be incorporated into DNA instead of thymine & base pairs with adenine
* tautomeric shift:
* _____ form: binds with adenine
* _____ form: binds with guanine
* promotes the change of an AT base pair into a GC base pair

short, high, X, gamma, free radicals, deletions, breaks, oxidized

ionizing radiation:

* _____ wavelength and _____ high energy
* _____-rays and _____ rays
* produces chemically reactive molecules known as _____ _____
* can cause:
* base _____
* single-stranded and double-stranded _____ in the DNA backbone
* crosslinking
* _____ bases

long, low, UV, thymine dimers

nonionizing radiation:

* _____ wavelength and _____ high energy
* _____ light
* causes the formation of _____ _____ (do not base-pair properly during DNA replication → produce a mutation when the DNA strand is replicated)

thymine dimer

two adjacent thymine bases in DNA strand that have become covalently linked because of nonionizing radiation

Ames test

a test using strains of a bacterium, Salmonella typhimurium, to determine if a substance is a mutagen

Salmonella typhimurium, histidine, histidine, histidine histidine, wild-type

Ames test

* uses strains of a bacterium, _____ _____, that cannot synthesize the amino acid _____
* these strains contain a point mutation within a gene that encodes an enzyme required for _____ biosynthesis (mutation renders the enzyme inactive)
* the bacteria cannot grow on petri plates unless _____ has been added to the growth medium
* second mutation (reversion)
* restores the ability to synthesize _____
* cause a reversion back to the _____ condition
* the Ames test monitors the rate at which the second mutation occurs, thereby indicating whether an agent increases the mutation rate above the spontaneous rate

photolyase

an enzyme found in bacteria, fungi, most plants, and some animals that can recognize and split thymine dimers, which returns the DNA to its original condition

photoreactivation

a type of DNA repair mechanism of thymine dimers that involves photolyase and requires light

thymine dimers, light

photolyase/photoreactivation:

* enzyme called photolyase recognizes _____ _____ and splits them, returning the DNA to its original condition
* repair mechanism requires _____ (photolyase contains two light-sensitive cofactors)

alkyltransferase

an enzyme that can remove methyl or ethyl groups from guanine bases

guanine, alkylating, suicide

alkyltransferase:

* enzyme that can remove methyl or ethyl groups from _____ bases that have been mutagenized by _____ agents such as nitrogen mustard and EMS
* “_____” enzyme: action permanently inactivates alkyltransferase, which means it can be used only once

base excision repair

a type of DNA repair in which a modified base is removed from a DNA strand. Following base removal, a short region of the DNA strand is removed and then resynthesizes using the complementary strand as a template.

DNA N-glycosylase

an enzyme that can recognize an abnormal base and cleave the bond between it and the sugar in the DNA backbone

AP endonuclease

a DNA repair enzyme that recognizes a DNA region that is missing a base and makes a cut in the DNA backbone near that site

DNA N-glycosylase, AP endonuclease, uracil, AP, 3-methyladenine, methylguanine

base excision repair:

* _____ _____: recognizes an abnormal base and cleaves the bond between the base and the sugar
* _____ _____: recognizes a missing base and cleaves the DNA backbone, removing the sugar/phosphate
* eliminate abnormal bases:
* _____
* _____ sites
* _____
* _____

nucleotide excision repair

a DNA repair system in which several nucleotides in the damaged strand are removed from the DNA and the undamaged strand is used as a template to resynthesizes a normal strand

thymine dimers, UvrA, UvrB, UvrC, UvrD

nucleotide excision repair:

* can repair many different types of DNA damage, including _____ _____ (caused by UV light), chemically modified bases, missing bases, and certain types of crosslinks
* requires four key proteins: _____
* recognize and remove a short segment of a damaged DNA strand

transcription-coupled repair

special type of nucleotide excision repair that recognizes thymine dimers and removes RNA polymerase from the damages region of the DNA during transcription

nucleotide excision repair, thymine dimer

transcription-coupled repair:

* special type of _____ (3 words)
* TRCF functions as a helicase and removes RNA polymerase from the damaged region (_____ _____)
* several biological advantages:
* active genes are more _____ packed
* _____ may make DNA more susceptible to damage
* regions more likely to be important for survival

base pair mismatch

a DNA abnormality in which two bases opposite each other in a double helix do not conform to the AT/GC rule

mismatch repair system

a DNA repair system that recognizes base pair mismatches and repairs the newly made daughter strand that contains the incorrect base

mismatched, MutS, MutL, MutH

mismatched repair:

* correction of _____ bases after DNA synthesis
* E. coli proteins:
* _____
* _____
* _____