DNA mutations

in a natural population, _________ is most common phenotype and some genes have multiple of these alleles prevalent

wild-type

______________ changes wild-type mutation to some new variation (moves away from wild-type)

forward mutation

__________ ________ takes the mutant back to the wild-type phenotype

reverse mutation

_____________ ____________ is an exact fix alteration of of mutated base back to wild-type sequence

true reversion

___________ _________ mutation re-creates original phenotype without correcting mutation itself

second-site reversion

Second-site reversion is also called ___________ __________

suppressor mutation

second-site reversion suppresses the effect of the _______ mutation

first

______________ __________ has the 2nd mutation in same gene as 1st mutation

intragenic suppressor

_____________ __________ mutations are in different gene

intergenic suppressor

forward mutation example

_________ _______ uses bacterial tester strains to screen for chemical mutagens

Ames test

In Ames test, salmonella cells are histidine _____________

auxotrophs

Salmonella cells are used in ames test because they are ____________ to mutation by chemicals

sensitive

___________ require chemicals because they are unable to synthesize in growth medium

auxotrophs

In Ames test you add suspected mutagen to cells, if it is a mutagen _____________ ____________ will produce his ____________ colonies

revertant mutation, prototrophic

_____________ can synthesize all needed metabolites and are grown on minimal medium

prototrophic

In Ames test you add suspected mutagen to cells, if it is not a mutagen there will be _______ growth meaning it __________ revert back to wild-type

no, cannot

Ames test

In Ames test, S9 extract is added to the strain and it a ___________ enzyme

liver

In an Ames test, many chemicals are not ___________ themselves

mutagenic

In an Ames test, the strain is converted to mutagens by ______________ _______________ pathways in liver

enzymatic detoxification

In the Ames test, you add the test chemical to ________ of plate

middle

In a Ames test, the mixture is plated on a medium lacking __________

histidine

In a Ames test, you can have negative control which is a plate with _______________ solvent

nonmutagenic

In a Ames test, the number of __________ colonies measure of mutagen potency

revertant

In a Ames test, the ___________ control has few colonies with some spontaneous mutations

negative

______________ _________ ____________ is an unusual form of mutation that can cause several human genetic disorders

trinucleotide repeat expansion

In normal individuals, certain genes and chromosomes locations contain regions with _____________ _________

trinucleotide repeats

In normal individuals, sequences are transmitted from parent to offspring _________ mutation

without

trinucleotide repeat expansion results when repeat copy number ___________ above critical size

increases

there are unusual features of trinucleotide repeat expansion disorders, one of which is the severity of disease can worsen in future generations, this is called ______________

anticipation

_____________ is when the repeat range is just above normal to many

premutation

_______________ is when the repeat number expands beyond premutation

full mutation

there are unusual features of trinucleotide repeat expansion disorders, one of which is severity depends on __________ from mother or father

inheritance

there are unusual features of trinucleotide repeat expansion disorders, but the cause is not well understood however increased repeats alter DNA structure (_________ _______ ___________) and can lead to replication error

stem loop formation

Formation of hairpin loop

mechanism of trinucleotide repeat expansion

The establishment of a mutation in both DNA strands occur by first, during ___________, DNA polymerase erroneously adds a C instead of a T, creating a mismatch

replication

The establishment of a mutation in both DNA strands occurs by after the mismatch, the mutation is present in ________ strands of one of the DNA molecules following replication

both

The establishment of a mutation in both DNA strands occurs by after the mutations are present in both strands, the ___________ is replicated

mutation

______________ ___________ is changes in DNA structure that result from abnormalities in biological processes

Spontaneous mutations

spontaneous mutations have the following common causes: _________________, _________________, __________________, __________________, _________________

Abberant recombination, Abberant segregation, DNA replication errors, Toxic metabolic products, Transposable elements

____________ ___________ is an abnormal crossing over which may cause deletions, duplications, translocations, inversions

Abberant recombination

_____________ __________ is an abnormal chromosome segregation may cause aneuploidy or polyploidy

Abberant segregation

_________ ____________ ___________ is a mistake by DNA polymerase may cause point mutation

DNA replication errors

____________ ___________ ___________ are products of normal metabolic processes may be chemically reactive agents that can alter DNA structure

Toxic metabolic products

_____________ ____________ can insert themselves into genes

Transposable elements

__________ _________ changes caused by environmental agents

Induced mutation

Induced mutations have the following common causes: _____________ and ______________

chemical agents in DNA structure, Physical agents

___________ ________ ____________ are chemical substances that may cause changes

Chemical agents in DNA structure

___________ _________ are UV lights, X-rays that can damage DNA

Physical agents

Spontaneous mutations are __________ replication

unfaithful

In spontaneous mutations mutant E. coli strains are ___________

mutators

mutators make more mistakes during ______________

DNA replication

____________ rates are higher than wild type

mutation

Genes that are defective in mutator strains: __________ encodes subunit of DNA pol. III and genes encoding proteins for ________ repair mechanisms

mutD, mismatch

mutD is a component needed for 3’ to 5’ __________ _______

exonuclease activity

In spontaneous mutations, DNA bases themselves cause some _________ mistakes

replication

Spontaneous mutation have have DNA bases that normally exist in 1 or 2 possible forms or __________

tautomers

The changing from normal form to rare form is called ____________

tautomerization

In thymine the common form is _______ or _________ form

keto, lactam

In thymine the rare form is when keto switches to __________ or __________ form

enol, lactim

The thymine enol form pairs naturally with ________ instead of adenine

guanine

In thymine, if T in _______ form during replication, then G inserted in place of A

enol

The error in enol thymine if uncorrected, replication will keep going, resulting in a __________

mutation

Guanine also has ________ and ________ forms

keto, enol

In Guanine, the rare enol form of G pairs with normal ______

T

Adenine has _______ and _________ form

amino, imino

The _______ form of adenine pairs with T

amino

The _______ form of adenine pairs with C

Imino

In Adenine, if there is an A in the imino form in DNA, polymerase will insert ______ instead of T

C

Cytosine also has two tautomeric forms: ____________ and ___________

amino, imino

In spontaneous mutations, _______ ____________ also can cause insertion or deletion of 1 or more bases

DNA replication

The changing of of bases, if in a middle of a coding region will change the reading frame from that point on, this is called ___________ _________

frameshift mutation

Frameshift mutations occur when DNA polymerases ______ every now and then

slip

_________ _______ is when a base in 1 strand fails to pair with base in a complementary strand (likely in stretches of DNA with 1 base repeated several times)

looping out

In spontaneous mutations, if a base in template strand loops out, 1 too few bases will be incorporated in progeny strand this would cause a 1 bp ___________

deletion

In spontaneous mutations, if a base in progeny strand loops out, 1 too few bases will be incorporated in progeny strand this would cause a 1 bp ___________

insertion

In spontaneous mutations, mutations can occur by mechanisms other than in ________ ____________

DNA replication

Spontaneous mutation bases, especially cytosine, have slight tendency to lose amino groups is called ______________

deamination

In spontaneous mutation, when C is deaminated, it receives carbonyl oxygen in place of its amino group and it converts to ________ which means it now pairs with ______ instead of G

uracil, A

In spontaneous mutations, Adenine also can be deaminated, it yields base termed ____________ and it now pairs with ________ instead of T

hypoxanthine, C

In spontaneous mutations, deamination can potentially cause mutation because new ________ with new ________ properties is created

base, pairing

The most common deamination is ______ converting to ______, although this does NOT usually lead to mutation

C, U

In spontaneous mutations, cells have a mechanism for removing uracil from DNA, this is seen as a __________ and uses the enzyme ________________

mistake, uracil-DNA-glycosylase

uracil-DNA-glycosylase cuts bond between _______ and ___________, it then removes _______ leaving behind DNA nucleotide without base and another enzyme will replace base by pairing with opposite strand

U, deoxyribose, U

In spontaneous mutations, certain mutations are recognized by _______ ____________

DNA glycosylase

DNA glycosylase breaks glycosidic bond between damaged base and sugar and it leaves an ________ or __________ site (______ ________)

apurinic, apyrimidic, AP site

In spontaneous mutations, AP site recognized by _________ _____________

5’ AP endonuclease

5’ AP endonuclease _________ DNA strand on 5’ side of AP site

cuts

The cut termed _________, creates free end within DNA strand

incision

The cutting of the DNA strand signals other enzymes to complete _________ process

excision

After the excision process, _______ _________ adds in new nucleotides

DNA polymerase 1

after the new nucleotides are added, __________ ________ repairs nick (forms phosphodiester bond)

DNA ligase

Spontaneous mutations - repairing damaged bases

Spontaneous mutations to our DNA happens _______ in every human cell

daily

In spontaneous mutations, DNA of many organisms contains a small number of modified bases, the most common is _____________ (which also pairs with G)

5-methylcytosine

5-methylcytosine is not exactly like C, the sites with __________ can be hot spots for spontaneous mutation via deamination

5mC

Deamination of C results in U which is easily ___________ and ___________ but this is not so with 5mC deamination

recognized, removed

Since T is normal base in DNA it is not ____________ as mutation

recognized