Origins of Mutations and DNA Replication/Repair

Question 1

Name three common DNA lesions

Answer 1

Depurination (lost of purines)
Deamination (most common is cytosine to uracil)
Pyrimidine Dimers (dimerization of thymine)

Question 2

What kind of mutations have variations in nucleotide sequence that might be as small as a single base pair change

Answer 2

Gene Mutation

- rare event (10^-10)

Question 3

What kinds of mutations have rearrangements, deletions, or duplications of chromosomal regions?

Answer 3

chromosomal mutation

- more often than gene mutations, not still not very frequent (6x10^-4)

Question 4

What kind of mutations have surplus or loss of chromosomes

Answer 4

genomic mutation

- most frequent type of mutations (10^-2)

Question 5

What kind of mutations change methylation of DNA or in the modification of histone proteins that contribut to control of gene expression?

Answer 5

mutations that impact chromatin

Question 6

What are point mutations?

Answer 6

exchange of one nucleotide for another

Question 7

What are the four types of point mutations?

Answer 7

1) silent
2) missense
3) nonsense
4) RNA processing mutant

Question 8

Which type of point mutation is this?

change in nucleotide sequence that changes the amino acid sequence

Answer 8

missense

Question 9

Which type of point mutation is this?

change in nucleotide sequence that does not affect the resulting amino acid sequence

Answer 9

silent

Question 10

Which type of point mutation is this?

change in nucleotide sequence that results in generation of a stop codon

Answer 10

nonsense

Question 11

What does RNA processing mutant affect?

Answer 11

RNA splicing

Question 12

What are the three processes that can lead to small insertions or deletions?

Answer 12

1) incorrect recombination
2) strand slippage during replication
3) intercalating agents

Question 13

What’s incorrect recombination?

Answer 13

misalignment during MEIOSIS that leads to unequal crossover causing insertions or deletions of genetic material
- usually occur when there’s repetitive sequence

Question 14

What is strand slippage?

Answer 14

occurs during REPLICATION, usually with repetitive sequence as well
- newly synthesized DNA strand may loop out in a single-stranded form. the piece slips back along the template strand. the next of replication will have a repeated sequence

Question 15

What kind of mutation is this? What can result?
occurs when an insertion or deletion of nucleotides that is not a multiple of three, affects codon structure downstream of the mutation

Answer 15

frameshift mutations

- completely different protein product

Question 16

What process is a major source of chromosomal and genome mutations?

Answer 16

meiosis

Question 17

What process leads to recombination of genetic material leading to new combinations?

Answer 17

meiotic crossover

Question 18

What is the process that forms haploid germ cells?

Answer 18

meiosis

Question 19

In which phase of meiosis do chromosomes condense and is visible by light microscope?

Answer 19

prophase

Question 20

In which phase of meiosis do chromosomes position themselves at the equator of the cell?

Answer 20

metaphase

Question 21

What is non-disjunction?

Answer 21

incomplete separation of chromosomes in anaphase

• source of genetic disease
• leads to surplus or missing chromosomes in germ cells

Question 22

In which chromosomes are trisomy observed? What are the names of the diseases associated with each of them?

Answer 22

Patau - 13
Edward - 18
Down - 21

Question 23

What are the six types of DNA repair strategies employed by the cell?

Answer 23

1) proofreading activity of DNA Pol
2) strand-directed mismatch repair
3) base excision repair
4) nucleotide excision repair
5) non-homologous end-joining
6) homologous end-joining

Question 24

Which type of DNA repair strategy is this?
A glycosylase removes the base, leaving the sugar-phosphate backbone intact. AP endonuclease then recognizes that a base is missing and cuts the sugar-phosphate backbone on one side of the missing base. Then DNA phosphodiesterase removes the deoxyribose phosphate group and DNA polyermerase and DNA ligase fills the gap.

Answer 24

Base excision repair

• there are different glycosylases that recognize different types of damaged bases
• most common is replacing uracil back with cytosine (deamination)

Question 25

Which type of DNA repair strategy is this?

DNA repair enzymes recognize distortions and remove the incorrect base pair and ‘chew back’ the DNA to the nearest nick

Answer 25

strand-directed mismatch repair

Question 26

Which type of DNA repair strategy is this?
once a distortion is detected, a helicase seperates the two strands and the phosphodiester backbone of the defective strand is cut on either side of the lesion. The gap is filled by DNA polymerase and DNA ligase

Answer 26

nucleotide excision repair

Question 27

Defect in which DNA repair mechanism causes HNPCC or Lynch syndrome?

Answer 27

strand-directed mismatch repair

Question 28

Defects in which DNA repair mechanism results in xeroderma pigmentosum?

Answer 28

nucleotide excision repair

Question 29

Which type of end-joining repair do not result in loss of nucleotides?

Answer 29

homologous end-joining

- uses recombination process to repair, this is possible because somatic cells are diploid

Question 30

Which type of end-joining result in loss of nucleotides leading to permanent changes?

Answer 30

non-homologous end-joining

- double-strand break and the two ends are joined together (no matching of base pairs at all)

Question 31

What chemotherapeutic agent is often used in treatment of Hodgkin’s lymphoma?
- it’s a pro-drug that is converted to phosphoramide mustard in the liver, which is a intercalating agent

Answer 31

Cyclophosphamide

Question 32

What chemotherapeutic agent is an analogue of cytidine that contains arabinose in place of ribose?
- the active form competes with dexoynucleotides for binding to DNA Pol thus DNA replication and repair are blocked

Answer 32

cytarabine