Chapter 18 conceptual

Nonsense suppressors, which are described in solved problems s1, tend to be very inefficient at their job of allowing readthrough of a stop codon. How would it affect the cell if they were efficient at their job?

An efficient nonsense suppressor would probably inhibit cell growth because all of the genes that have their stop codons in the correct location would make proteins that would be too long. This would waste cellular energy, and in some cases, the elongated protein may not function properly

Missense mutation

Appropriate

imino form of A binds to

C

rare enol form of thymine binds to

G

5'-GGACTAGATAC-3': 5'-GAACTAGATAC-3'

G-->A is a transition

What type of mutations would 5-Bromouracil cause

G-->A mutations, which are transitions

How would nucleotide excision repair be affected if one of the follwing proteins was missing? DNA polymerase

If DNA polymerase was missing, the repair system could identify the damaged segment, make cuts in the damaged strand, and unwind the damaged and undamage strands to remove the damaged segment, but it could not synthesize a complementary strand using hte undamaged strands as a template

enol form of G

T

5'-GGACTAGATAC-3': GGACTAGAGAC

T-->G is a transversion

TNRE are associated with several different inherited disease. When TNRE eerts its dtrimental effect by producing a glutamine stretch, are the following statements true or false? -TNRE is within the coding sequence of the gene

True

what happens to sequence of DNA during TNRE

a trinucletide repeat sequence gets longer

rare imino form of cytosine binds to

adenine

Intragenic suppressor

appropriate

Similarities of nucleotide excision repair and mismatch repair systems

both recognize an abnormality in the DNA and excise the abnormal strand. Normal strand is then used as a template to synthesize a complementary strand of DNA.

What types of mutations would proflavin cause?

small additions or deletions, which may result in frameshift mutations.

Are mutations random event?

spontanous mutaitons can occur in any gene and do not involve exposure of the organism to a particular environemnt that selects for specific types of mutation. Certain regions may be more predisoposed to being mutated.

What does a suppressor mutation suppress?

suppresses the phenotypic effects of some other mutation

Anticipation may depend on...

the sex of the parent with the TNRE

Explain how a mutagen can interfere with DNA replication to cause a mutation. Give two examples.

thymine dimer can interfere with DNA replication because DNa polymerase cannot slide past the dimer and add bases to the newly growing strand. Alkylating mutagens such as a nitrous acid will cause DNA replicatoin to make mistakes in the base pairing. For example, an alylated cytosine will base pair with adenine during DNA replication, thereby creating a mutation inteh newly made strand. A third example is 5-bromouracil, which is a thymine analogue. It may base pair with guanine instead of adenine during DNA replication

know the difference between transversion and transition

transversion purine changes to pyridine, or pyridine changes to purine

Lactose permease is encoded by the LacY gene of the lac operon. A mutation occured at codon 64 that changed the normal glycine codon nto a valine codon. The mutatnt lactose permease is unable to function. However, a second mutaiton, which changes codon 50 from an alanine codon to a theronine codon, is able to restore funciton. Are the following terms appropriate or inappropriate to describe this second mutation?

...

Segment of DNA has the following sequence TTGGATGCTGG AACCTACGACC -What would be the sequence immediategly after the reaction with nitrous acid? Let the letters H represent hypoxanthine and U represent Uracil

A turns to H, C becomes U TTGGHTGUTGG HHUUTHUGHUU

What type of mutaiton would you expect Nitrous acid to cause?

A-->G, and C-->T... transition mutaitons

If a mutagen causes bases to be removed from nucleotides within DNA, what repair system would fix this damage?

Excision repair systems could fix this damage. Homologous recombination repair could fix the damage

TNRE are associated with several different inherited disease. When TNRE eerts its dtrimental effect by producing a glutamine stretch, are the following statements true or false? -- The trinucleotide sequence is CCG

False, CCG is a codon for proline

TNRE are associated with several different inherited disease. When TNRE eerts its dtrimental effect by producing a glutamine stretch, are the following statements true or false? -TNRE prevents RNA polymerase from transcribing the gene properly

False; the TNRE is snot within the proomter, ti is within teh coding sequence

Explain two ways that a chromosomal rearrangement can cause a position effect

One possibility is that a translocation may move a gene next to a hterochromatic region of another chromosome and thereby diminish its expression or it could be moved next to a euchromatic region and increase its expression (TRANSLOCATION). Another possibility is that the translocation breakpoint may move the gene next to a new promoter or regulatory sequences that may now influence the gene's expression (INVERSION).

Silent, missense, nonsense, or frameshift? ATGGGACTAGATACC -->ATGGGTCTAGATACC

Silent, same amino acid is encoded by GGA and GGT

With regard to TNRE, what is meant by the term anticipation?

TNRE expands even further in future generations. Anticipation may depend on the sex of the parent with the TNRE

TNRE are associated with several different inherited disease. When TNRE eerts its detrimental effect by producing a glutamine stretch, are the following statements true or false? -the trinucleotide sequence is CAG

True, CAG is a codon for glutamine

What can repair this defect caused by nitrous acid?

excision repair systems could remove the defect and replace it with the correct base

imino and enol

forms are rare

give an eample of a mutagen that can change cytosine to uracil.

nitrous acid can change a cytosine to uracil. DEAMINATION

Spontaneous mutations

originates within a living cel due to spontaneous changes in cucleotide strucutre, errors in DNA replication, or products of normal metabolism that may alter the structure of DNA

UV light causes what mutaitons?

produces thymine dimers

Silent, missense, nonsense, or frameshift? ATGGGACTAGATACC -->ATGGGACTAAGATACC

Frameshift, extra base is inserted into the sequence

How would nucleotide excision repair be affected if one of the follwing proteins was missing? UvrA

If UvrA was missing, the repair system would not be able to identify a damaged DNA segment

How would nucleotide excision repair be affected if one of the follwing proteins was missing? UvrC

If UvrC was missing, the repair system could identify the damaged segment, but it would be unable to make cuts in the damaged DNA strand

How would nucleotide excision repair be affected if one of the follwing proteins was missing? UvrD

If UvrD was missing, the repair system could identify the damaged segment and make cuts in the damaged strand, but it could not unwind the damaged and undamaged strands and thereby remove remove the damaged segment

Discuss consequences of germ line versus a somatic mutation.

If mutaiton within germ line is passed to an offspring, all cells of the offsprings body will cary the mutaiton. Somatic mutation affects only the somatic cell in which it originated and all of the daughter cells that the somatic cell produces. If a somatic mutation occurs early during embyronic development, it may affect a fairly large region of the organism germ line are more harmful usually, sometimes beneficial

How would Up promoter mutation affect the amount of functional protein that is expressed fom a gene?

Increase the amount of functional protein

How would Missense mutation affect the amount of functional protein that is expressed from a gene?

May or may not affect protein function, depending on the nature of the amino acid subsitution and whether the substitution is in a critical region of the protein

During mismatch repair, why is it nedcessary to distinguish between the template strand and hte newly made daughter strand? How is this accomplished?

Mismatch repair is aimed at eliminating mismatches that may have occured during DNA replication. In this case, the wrong base is in the newly made strand. The binding of MutH, which occurs on a hemimethylated sequence, provides a sensing mechanism to distinguish between the unmethylated and methylated strands. In other words, MutH binds to the hemimethylated DNA in a way that allows the mismatch repair system to distinguish which strand is methylate and which is not.

Silent, missense, nonsense, or frameshift? ATGGGACTAGATACC -->ATGCGACTAGATACC

Missense, different amino acid is encoded by CGA and GGA

Silent, missense, nonsense, or frameshift? ATGGGACTAGATACC -->ATGGGACTAGTTACC

Missense, different amino acid is encoded by GTT and GAT

When DNA N-glycosylase recognizes thymine dimers, it detects only the thymine located on the 5' side of the thymine dimer as being abnormal. explain steps whereby thymine dimer is repaired by the consecutive actions of DNA N-glycosylase, AP endonuclease, and DNA polymerase

N-glycosylase first make a cut between the base and the sugar. This releases the thmine base from the nucleotide to which it was direclty atached but the thymine would still be connected to the adjacent thymine (3'). AP endonuclease would then make a nick in this DNA strand, and DNA polymerase would remove the abnormal region and at the same time replace it with normal nucleotides. Finally, the strand would be sealed by DNA ligase.

Can the follwoing be described as a position effect? -A point mutation at the -10 position in the promoter region prevents transcription.

No, the position of the gene has not been altered

Intergenic suppressor

Not appropriate, becausae the second mutation is in the same gene as the first mutation

Reversion

Not appropriate. because the second mutation is at a different codon

X-rays strike a chromosome in a living cell and ultimately cause the cell to die. Did the X-rays produce a mutaiton? Explain why or why not.

X-rays did not produce a mutation, because mutation is a heritable change in genetic material. X-rays killed the cell, so changes were not passed down.

Can the follwoing be described as a position effect? --A translocation places the coding sequence for a muscle-specific gene next to an enhancer that is turned on in nerve cells.

Yes, the expression ofa gene has been altered becasue it has been moved to a new chromosomal location

Can the follwoing be described as a position effect? -An inversion flips a gene from the long arm of chromosome 17 (euchromatic) to the short arm (heterochromatic)

Yes, the exxpression of a gene has been altered because it has been moved to a new chromosomal location

Most forms of cancer are caused by environmental agents that produce mutaitons in somatic cells. Is an individual with cancer considered a genetic mosaic?

Yes. cancerous tissue contains gene mutations that are not found in noncancerous cells of the body

With regard to the repair of double strand breaks, what are the advantages of homlogous recombination repair vs NHEJ

because sister chromatids are genetically identical, advantage of homologous recombination is that it can be an error-free mechanism to repair a DSB Disadvantage: occurs only during the S and G2 phase of cell cycle in eukaryotes or following DNA replication in bacteria Advantage of NHEJ: does involve the participation of sister chromatid, so it can occur at any stage of cell cycle Disadvantage of NHEJ: can result in small deletions in region that has been repaired. Quick but error prone repair mechanism, HR is more accurate but limited to certain stages

hot spots

certain regions of a gene that are more likely to mutate than other regions- can occur within a single gene. also, some genes are larger than others

2 examples of mutations of sequences that are outside the coding sequence and are important for gene expression. How can a mutaiton change these sequences and thereby alter gene expression?

consensus sequences for many bacterial promoters are -35 and -10 TATAAT box at -10 TTGACA at -35 -35 region is recognized by CREB protein.. if changed may not be recognized and adjacent gene would not be regulated properly in the presence of cAMP

Underlying genetic defect that causes xeroderma pig mentosum?

defect in one of the genes that encode a polypeptide involved with nucleotide excision repair. defective in repairing dna abnormalities such as thymine dimers and abnomal bases

Differences between the nucleotide excision repair and mismatch repair systems

differ in the types of abnormalities they detect. mismatch repair system detects base pair mismatches, while the excision repair system recognizes thymine dimers, chemically modified bases, missing bases, and certain types of crosslinks. Mismatch repair system operates immediately after DNA replication. allowing it to distinguish between the daughter strand (which contains the wrong base) and the parental strand. The excision repair system ccan operate at any time in the cell cycle.

proflavin causes what type of mutations

frameshift

Induced mutations

from outside the cell may be physical agents such as UV light or X rays or chemicals that act as mutagens

AT base pair changes to a GC pair. This causes a gene to encode a truncated protein that is nonfunctional. An organism that carries this mutation cannot survive at high temperatures. Make a list of all genetic terms that could be used to describe this type of mutation.

gene mutation, point mutation base substitution transition mutation deleterious mutaiton mutant allele nonsense mtation conditional mutation tempuerature sensitive lethal mutation

Both spontaneous and induced mutations may cause a

harmful phenotype such as a cancer. Inducd are avoidable if the individual can prevent exposure to environmental agent that acts as a mutagen

if someone was mildly affected with TNRE disorder, what issues would be important when considering possible effects in future offspring?

he or she might be concerned that an epansion of the repeat might occur during gamete formation yielding offspring more severely affected with the disorder, a phenomenon called anticipation.

HETERO CHROMATIC VS EUCHROMATIC

hetero is transcriptionally inactive

What are the two main mechnaisms by which cells repair double strand breaks? Briefly describe each one.

homologous recombination and nonhomologous end joining (NHEJ).

difference between an intragenic and an intergenic suppressor?

intragenic are within the same gene as the first mutation intergenic are in another gene

tautomeric shift

isomers of bases that differ in position of atoms and bonds between atoms

How would mutation that affects splicing affect the amount of functional protein that is expresed from a gene?

may affect protein function if the alteration in splicing changes an exon in the mRNA that results in a protein with a perturbed structure

Draw and explain how alkylating agents alter the structure of DNA.

methyl or ethyl group to a base within DNA presence of the alkyl group disrupts the proper base pairing between the alkylated base and the normal base in the opposite DNA strand

A change in DNA sequence caused by a mistake made by DNA polymerase would be fixed by...

mismatch repair

Is a random mutation more likely to be beneficial or harmful? Explain you answer.

more likely to be harmful. genes within each species have evolved to work properly. functional promoters, coding sequences, terminators

What is the difference between the mutation rate and the mutation frequency?

mutuation rate is hte number of new mutations per gene per generation. The mutation frequency is the number of copies of a mutant gene within a population divided by the total number of copies of that gene. The mmutation frequency may be much higher than the mutation rate if new mutations acumulate within a population over the course of many generations.

keto form of tautomers

normally present in DNA

Which mechanism of DNA repair would be used for A change in the structure of a base caused by a mutagen in a nondividing eukaryotic cell?

nucleotide excision repair

In the treatment of cancer, the basis for many types of chemotherapy and radiation therapy is that mutagens are more effective at killing dividing cells than nondividing cells. Explain why. What are possible harmful side effects of chemotherapy and radiation therapy?

number of mutations accumulates in dividing cells side effects: can be cancerous, other cells besides cancer cells are dividing too

How would Nonsense mutation affect the amount of functional protein that is expressed from a gene?

probably inhibit protein function, particularly if it was not near the end of the coding sequence

A thymine dimer in the DNA of an actively dividing bacterial cell would be fixed by

recombinational repair and nucleotide excision repair

hoomologous recombination

segment of an undamaged sister chromatid is used as a template to repair a DSB in the damaged sister chromatid. See figure 18.21

5'-GGACTAGATAC-3': GGACTAGTAC

single nucleotide deletion

TNRE

trinucleotide repeat expansion

Nonhomologous end joining (NHEJ)

two broken ends of DNA are simply pieced back together by proteins and end processing

How can symptoms of xeroderma pigmentosum be explained by the genetic defect?

vey sensitive to environmental agents such as UV light. develop pigmentation abnormalities and premalignant lesions, and have a high predisposition to skin cancer