Chapter 2 - Molecular Mechanisms of DNA Damage and Repair

Question 1

What type on damage does ionizing radiation induce?

Answer 1

Single strand breaks
Double strand breaks
Crosslinks

Question 2

Which strand breaks are most lethal?

Answer 2

Double strand breaks

Question 3

Double strand breaks are repaired in two ways?

Answer 3

Homologous recombination

Nonhomologous recombination

Question 4

What is the difference between homologous and nonhomologous recombination?

Answer 4

Homologous recombination happens mainly in S/G2 phases and uses a unbroken template to copy

Nonhomologous recombination happens in G1 and does not use a template.

Question 5

What letters are pyrimidines?

Answer 5

Thymine and cytosine (single ring group)

Question 6

What letters are purines?

Answer 6

Guanine and adenine (Double ring group)

Question 7

Single strand breaks do what biologically?

Answer 7

Not much

Maybe mutations

Question 8

Double strand breaks do what biologically?

Answer 8

Cell death
Carcinogenesis
Mutations

Question 9

Which happens more often: Double strand breaks or single strand?

Answer 9

Single strand - 96% of the time

Question 10

What are spurs and blobs?

Answer 10

The type (size) of track that a particulate or EM took when breaking the DNA… aka the size of the deposition of radiation

The size of the deposition determines the size or number of base pairs affected. AKA Clustered lesions

Question 11

Spurs are?

Answer 11

3 OH pairs

Question 12

Blobs are?

Answer 12

12 OH ion pairs

Question 13

What is a clustered lesion?

Answer 13

The size of the DNA damage in base pairs

Question 14

What can you use to measure the amount of strand breaks in DNA?

Answer 14

PFGE
- Double strand breaks only

Single-Cell electrophoresis

• can look at individual cells
• Can look at both single strand break and double

DNA damage-induced nuclear foci
- Looks for complexes that repair proteins and quantitate them

Question 15

What is the difference between intra-strand crosslink and inter-strand crosslink?

Answer 15

Intra-strand crosslink leads to a block in DNA polymerase that is easily overcome

Inter-strand crosslink leads to a block in DNA polymerase that is not easily overcome.

Question 16

Phases of the cell cycle (mitosis)?

Answer 16

Interphase
Prophase 
Metaphase
Anaphase
Telophase

Question 17

What happens in interphase?

Answer 17

DNA duplicates

Chromosomes stay in their domains

Question 18

What happens in prophase?

Answer 18

Chromosomes condense
Centromeres apparent
Nuclear membrane disappears

Question 19

What happens in metaphase?

Answer 19

Chromosomes move to center

Spindles form

Question 20

What happens in anaphase?

Answer 20

Pulling apart chromosomes

Question 21

What happens in telaphase?

Answer 21

Uncoiling of DNA

Nuclear membranes return

Question 22

What is a telomere and how do they affect cells?

Answer 22

Telomeres are repeats of TTAGGG. This leaves a long tail of nothingness so that when the cell divides it cleaves the telomere and not the encoding DNA.

However, telomeres only have a certain amount of length and therefore once they are used up the cell quits replicating.

However, stem cells and cancer cells have telomerase which adds more telomere to the ends thus making the cell able to divide indefinitely.

Question 23

Radiation induced chromosome or chromatid aberrations are looked at in what phase?

Answer 23

Metaphase

Question 24

Radiation induced chromosome aberrations are noted if radiation is induced when?

Answer 24

Early interphase

Question 25

Radiation induced chromatid aberrations are noted if radiation is induced when?

Answer 25

Late interphase

Question 26

What are the three types of lethal aberrations described in this chapter?

Answer 26

Dicentric - Chromosome aberration
Ring - Chromosome aberration

Anaphase bridge - chromatid aberration

Pg: 27

Question 27

What is an acentric fragment?

Answer 27

Fragments of DNA with no centromere

Question 28

What two non-lethal aberations are described?

Answer 28

Symmetric translocation - A break in TWO different prereplicated chromosomes

Small interstitial deletion - Two breaks in the same arm of the same chromosome

Question 29

How can we look for the non-lethal aberrations?

Answer 29

FISH or chromosome painting

Question 30

How do non-lethal aberrations cause cancer?

Answer 30

Deletion of tumor suppressor genes

Activation of an oncogene

Question 31

Are interaction between breaks in different chromosomes random?

Answer 31

No— remember they are in domains so they interact within a probability with each other.

Question 32

Is there a good correlation between killed cells and cells with asymmetric exchange aberrations (dicentric and rings)?

Answer 32

YES so we can use that for estimating cells killed

Question 33

Is the incidence of most-radiation induced aberrations a function of dose?

Answer 33

YES… linear-quadratic

Question 34

Can we score aberrations from full body irradiation?

Answer 34

YES with lymphocytes from peripheral blood

Question 35

What is the lowest dose we can detect from scoring aberration in lymphocytes of the peripheral blood?

Answer 35

0.25 Gray = 25 Rads

Question 36

Why are dicentric aberrations considered unstable?

Answer 36

They are lethal to the cell and therefore do not pass on the aberrations

Question 37

Why are translocation aberrations considered stable?

Answer 37

They persist for many years because they are not lethal to the cell. They are passed on to the cells progeny.