FOM 5.2.1

Question 1

Who is the famous actress that used prophylactic surgery to reduce her risk of cancer upon finding out that she had a mutation in BRCA1 or BRCA2?

Answer 1

Angelina Jolie (Sean’s Queen)

Question 2

As doctors, we are concerned with survival. This often means we promote genomic stability. What might this adversely affect?

Answer 2

Our evolution as a species

Question 3

What is the difference b/t a somatic and germline mutation?

Answer 3

Somatic: only affects individual Germline: mutation in cells that produce gametes, offspring will have mutation

Question 4

What are three overarching sources of DNA damage?

Answer 4

Physical, chemical, copying errors

Question 5

A light-skinned woman of European descent (Miles’ mother) sits in direct sunlight for an hour, how many damaging events occurred in the DNA of a typical skin cell on her face?

Answer 5

4000 for normal humans (however, Miles’ mother is goddess and thus isn’t susceptible to mutations)

Question 6

What are the two types of chemical mutagens?

Answer 6

DNA adducts, free radicals

Question 7

What are two common results of DNA adducts?

Answer 7

altered base pairing and dsDNA breaks

Question 8

Cisplatin, a DNA cross-linking drug, can cause what two types of cross-links?

Answer 8

Intrastrand, Interstrand

Question 9

What makes UVB worse than UVA? What do both types of UV create?

Answer 9

UVB is in the range of maximum absorbance of DNA; both create ROS

Question 10

What type of mutation is produced by UV light?

Answer 10

thymidine (which is pyrimidine nt) dimers

Question 11

What type of mutations are caused by ionizing radiation?

Answer 11

ssDNA and dsDNA breaks

Question 12

What are the three steps of proofreading (which helps to reduce mistakes during DNA replication)?

Answer 12

Stop, Backtrack w/ a 3’-5’ exonuclease, Continue on again

Question 13

What are the 3 steps of DNA lesion repair?

Answer 13

1) Recognize lesion 2) Remove lesion 3) Fill in gap

Question 14

What are the two types of small lesions? What are the repair mechanisms for each?

Answer 14

Question 15

What are the three types of complex lesions? What are the repair mechanisms for each?

Answer 15

Question 16

What are the two repair methods for dsDNA breaks? Which is preferred?

Answer 16

Homologous recombination repair (preferred), Non-homolgous end joining

Question 17

What repair mechanism is disrupted in Lynch Syndrom (hereditary nonpolyposis colorectal cancer)?

Answer 17

mismatch repair, congenital absence of any one of the four proteins involved in repair

Question 18

What dz’d state is associated with defect in nucleotide excision repair?

Answer 18

Xeroderma Pigmentosum (XP)

Question 19

What dz’d state is associated with defect in ICL repair?

Answer 19

Fanconi’s anemia, a defect in one of the 13 proteins involved

Question 20

What the two main clinical manifestations/challenges of Fanconi’s Anemia?

Answer 20

Bone marrow failure and various forms of leukemia

Question 21

Homologous recombination is often referred to as what type of mechanism?

Answer 21

“Error-free”

Question 22

What two restricting factors of homologous repair?

Answer 22

cell cycle phase (S and G2), presence of template strand

Question 23

Along with having a defect in the ICL repair pathway, Fanconi’s anemia (FA) can have a defect in what type of repair?

Answer 23

Homologous recombination repair, which results in chromosome instability syndrome

Question 24

What are the main steps of non-homologous end joining (NHEJ)?

Answer 24

Recognition, DNA end blunting, end joining synthesis (resulting translocations are noted in a number of leukemias)

Question 25

If doctor’s tell both parents that a child shouldn’t be exposed to sunlight b/c it will increase severity, what type of mutation are they trying to prevent?

Answer 25

Pyrimidine dimers

Question 26

Loss of Repair = _____

Answer 26

Many mutations (duh… have you even been paying attention)

Question 27

What are two possible cellular results of chromosome instability syndromes?

Answer 27

cell death, neoplasia

Question 28

To exploit a BRCA mutation, what would be a good protein to inhibit? Why?

Answer 28

Poly ADP-ribose polymerase 1 (PARP1). By inhibiting this, DNA lesions will not be marked for repair, which will lead to increased amount of dsDNA breaks. Since homologous repair is absent in BRCA mutation, non-homologous repair is employed. Excessive NHEJ can lead to fatal DNA damage.