DNA Replication

Question 1

Telomerase activation: immortalization

Answer 1

Telomerase should only be expressed in dividing (mitotic) cells. Cancer cells can become immortalized by expressing telomerase.

Telomerase inhibitors are cancer therapy

Question 2

HIV Reverse Transcriptase

Answer 2

Reverse Transcriptase DNA polymerase

Treatment: Highly Active Anti-Retroviral Therapy (HAART)
Zidovudine (ZDV): Thymine analog. No 3’OH. Terminates Replication
Also 2’3’ DiDeoxynosine (DDI). lacks 3’OH. Terminates replication

Question 3

Herpes Simplex Virus (HSV)

Answer 3

HSV including varicella zoster (chickenpox), herpes zoster (shingles)

Treatment: Acyclovir (a Guanisine analog). DNA synthesis inhibition.
SELECTIVELY PHOSPHORYLATED by viral kinase. not phosphorylated in uninfected cells. uninfected cells not affected.

Question 4

Cytomegalovirus (CMV) Retinitis

Answer 4

causes blindness

Gancyclovir. Guanisine analog.
ELECTIVELY PHOSPHORYLATED by viral kinase. not phosphorylated in uninfected cells. uninfected cells not affected.

Question 5

Exogenous DNA damage

Answer 5

ionizing radiation. creates thymine dymers

environmental chemicals: hydrocarbos, aflatoxins cause depurination, deamination

Question 6

Endogenous DNA damage

Answer 6

ROS.
also from mistakes in DNA replication.
also from deamination of 5’methylcytosine

Question 7

Cancer drug resistance

Answer 7

Cancer resistance to Cisplatin (anti-cancer drug, induces apoptosis) by overexpressing ERCC1, gene encoding XP-F, an endonuclease involved in Nucleotide Excision Repair (NER patch repair)

ERCC1 is DNA marker for drug resistance.

Question 8

Colorectal Cancer (Hereditary nonpolypoisis Colorectal Cancer)

Answer 8

MER (Mismatch Excision Repair–patch) mutation. mutation in MLH1 or MLH2. proteins that detect mismatch in Mismatch Excision Repair (MER).
tissue that rapidly turns over, like epithelial cells lining colon, more susceptible to mismatch errors

Question 9

Xeroderma Pigmentosum

Answer 9

NER (Nucleotide Excision Repair–patch) mutation. inability to repair UV DNA damage.
cancerous lesions. progressive neuro, loss of sight, hearing. PCOD cancer. lifespan shortened by ~30 years

protect from UV exposure

Question 10

Cockayne syndrome

Answer 10

NER (Nucleotide Excision Repair–patch) mutation.
premature aging. neuro issues. no cancer.
RCC8 or ERCC6 mutation.

Question 11

Sickle Cell Anemia

Answer 11

polymorphism destroys MSII site in B-globin gene.

Question 12

Cystic Fibrosis

Answer 12

buildup of mucus in lungs. lung infections common. fatty stools (steatorrhea). diagnosed by positive sweat test.