Human Disease

Question 1

Describe the pathophysiology of Lesch-Nyhan Syndrome and associated symptoms.

Answer 1

A gene coding for an enzyme responsible for the recycling of purines does not function properly –> leads to an accumulation of low-solubility purines and high uric acid levels. Gout symptoms, hyperkinetic symptoms, moderate intellectual disability, poor muscle control, and self-mutilation. Symptoms usually appear in first year of life and almost entirely in males.

Question 2

Describe the pathophysiology of Gout and its symptoms.

Answer 2

Defect in enzyme leads to the accumulation of low-solubility purines, rise in serum uric acid, and deposition of uric acid crystals in joint fluid. Pain, redness, swelling at joints (most often metatarsal-phalangeal of big toe).

Question 3

Describe the mechanism of action of AZT.

Answer 3

Zidovudine (AZT) is a nucleoside analog reverse transcriptase inhibitor. As a thymidine analog it inhibits reverse transcriptase (eg. in HIV) from synthesizing DNA and incorporating it into the cell.

Question 4

Ultraviolet light damages DNA by catalyzing covalent linkage of adjacent _______.

Answer 4

Thymines

Question 5

Drugs which interfere with DNA function by intercalation are often used in _______.

Answer 5

Chemotherapy

Question 6

Describe how puromycin halts protein synthesis.

Answer 6

Puromycin, an antibiotic is a nucleotide that mimics the tRNA acceptor region and induces release of elongating peptide.

Question 7

45% of human gliablastomas occur with a mutation in the enzyme, ________________, which works to repair methylation damage to DNA.

Answer 7

O6-methylguanine-methyltransferase

Question 8

Base damages that do not distort DNA are repaired by _________.

Answer 8

Base excision repair (uses base-specific glycosylases to remove base)

Question 9

Base damage that distorts DNA is repaired by ___________.

Answer 9

Nucleotide excision repair (NER)

Question 10

Mismatch repair (MMR) repairs what damage?

Answer 10

Mismatches occurring during DNA replication.

Question 11

T/F: During nucleotide excision repair only the affected nucleotide is removed.

Answer 11

False. After unwinding by helicases, two endonucleases cut out a strand of DNA about 30bp long containing the wrong/damaged nucleotide.

Question 12

Xeroderma Pigmentosum is a condition associated with a defect in one of the two types of damage-recognition in NER. That type of recognition is: _______.

Answer 12

Global genome NER. Recognizes damage anywhere in the genome.

Question 13

Cockayne Syndrome, a neurodegenerative condition, is a associated with a defect in one of the two types of damage-recognition in NER. That type of recognition is: _______.

Answer 13

Transcription-Coupled NER. Recognizes damage w/in the transcribed region.

Question 14

MMR identification of the template (correct) strand along the lagging strand is achieved by _________.

Answer 14

Recognition of nicks in between Okazaki fragments.

Question 15

MMR identification of the template (correct) strand along the LEADING strand is achieved by _________.

Answer 15

Recognition of transient ribonucleotides in the replicated strand.

Question 16

Hereditary non-polyposis colorectal cancer (Lynch Syndrome) accounts for 5% of all cases of colon cancer and is attributable to defects in the genes responsible for ________.

Answer 16

Mismatch Repair (MMR)

Question 17

Osteogenesis imperfecta is cause by a change from glycine to ________. The triple helices of ________ are then unable to form the correct hydrogen bonds between _______ residues.

Answer 17

cystine, collagen, proline