Molecular Biology III

Question 1

What is the pathology associated with an adenosine deaminase deficiency?

Answer 1

Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase. This prevents DNA synthesis and decreases lymphocyte count; autosomal recessive (p.66)

Question 2

What is the clinical presentation of an adenosine deaminase deficiency?

Answer 2

SCID, an autosomal recessive condition (p.66)

Question 3

What is the pathology associated with Lesch-Nyhan syndrome?

Answer 3

Defective purine salvage owing to absence of HGPRT which converts hypoxanthine to IMP and Guanine to GMP. This results in excess uric acid production and de novo purine synthesis. X-linked recessive (p.66)

Question 4

What are some clinical features of Lesch-Nyhan syndrome?

Answer 4

Retardation, self mutiliation, aggression, hyperuricemia, gout, choreoathetosis (p.66)

Question 5

Which amino acids are only coded for by one codon?

Answer 5

Methionine (AUG), Tryptophan (UGG) (p.66)

Question 6

What is a nonsense DNA mutation?

Answer 6

Change resulting in an early stop codon (p.67)

Question 7

Name 3 differences between prokaryotic and eukaryotic DNA replication.

Answer 7

1.) Prokaryotes have a single origin of replication; eukaryotes can have many; 2.) Prokaryotes contain DNA Pol III (which elongates leading strand by adding deoxynucleotides to the 3’ end; 3.) Prokaryotes contain DNA Pol I which degrades RNA primer and replaces it with DNA (p.68)

Question 8

What is the function of single strand binding proteins?

Answer 8

Prevents strand from reannealing (p.68)

Question 9

What is the function of DNA topoisomerases?

Answer 9

To create nicks in the DNA helix to relieve supercoils created during replication (p.68)

Question 10

Which class of drugs inhibit prokaryotic topoisomerase II (or DNA gyrase)?

Answer 10

Fluoroquinolones (p.68)

Question 11

What is the function of primase?

Answer 11

To make an RNA primer on which DNA polymerase III can initiate replication (p.68)

Question 12

What is DNA Polymerase III?

Answer 12

Prokaryotic enzyme that elongates the leading strand by adding deoxynucleotides to the 3’ end. It elongates the lagging strand until it reaches the primer of the proceeding fragment. Contains 3’–> 5’ exonuclease activity and proofreads each added nucleotide. Synthesis: 5’ –> 3’; Proofreading: 3’ –> 5’ exonuclease (p.68)

Question 13

What is DNA Polymerase I?

Answer 13

A prokaryotic enxyme that degrades RNA primer and replaces it with DNA. It has the same functions as DNA Pol III but also excises RNA primer with 5’ –> 3’ exonuclease (p.68)

Question 14

What is DNA ligase?

Answer 14

Catalyzes the formation of phosphodiesterase bonds within a strand of double stranded DNA; joins Okazaki fragments (p.68)

Question 15

What is telomerase?

Answer 15

An enzyme that adds DNA to the 3’ end of chromosomes to avoid loss of genetic material with every duplication (p.68)

Question 16

Describe the process of nucleotide excision repair.

Answer 16

Single stranded DNA repair system where specific endonucleases release oligonucleotide containing damaged bases; DNA polymerase and ligase fill and reseal the gap (p.69)

Question 17

What types of errors are corrected by nucleotide excision repair (NER)?

Answer 17

Repairs bulky, helix distorting lesions (p.69)

Question 18

What condition is caused by a mutation in nucleotide excision repair?

Answer 18

Xeroderma Pigmentosum –> prevents repair of pyrimidine dimers due to UV light exposure (p.69)

Question 19

Describe the process of base excision repair.

Answer 19

Single stranded DNA repair system where specific glycosylases recognize and remove damaged bases and apurinic/apyrimidinic enconucleases cuts DNA at both apurinic and apyramidinic sites, removing the empty sugar and filling/ resealing the gap. This is important in the repair of spontaneous/ toxic deamination (p.69)

Question 20

Describe the process of mismatch repair.

Answer 20

Single stranded DNA repair system where newly synthesized strand is recognized, mismatched nucleotides are removed, gap is filled and resealed (p.69)

Question 21

What condition is caused by a mutation in Mismatch Repair?

Answer 21

Hereditary Nonpolyposis Colorectal Cancer (HNPCC) (p.69)

Question 22

Describe the process of non-homologous end joining.

Answer 22

Double stranded DNA repair system where 2 ends of DNA fragments are brought together to repair double stranded breaks. There is no requirement for homology (p.69)

Question 23

What condition is caused by a mutation in Nonhomologous end joining?

Answer 23

Ataxia Telangiectasia (p.69)

Question 24

How is protein synthesis terminated?

Answer 24

Stop codon is recognized by the release factor and the completed protein is released from the ribosome (p.73)

Question 25

Name two classes of antibiotics that act as protein synthesis inhibitors at the 30s subunit.

Answer 25

1.) Aminoglycosides –> bind 30s and inhibit formation of initiation complex. Cause mRNA misreading; 2.) Tetracyclines –> block aminoacyl tRNA from entering the acceptor site (p.73)

Question 26

Name two classes of antibiotics that act as protein synthesis inhibitors at the 50s subunit.

Answer 26

1. Chloramphenicol –> binds 50S and inhibits peptidyl transferase; 2.) Macrolides –> bind 50S and prevent release of uncharged tRNA after it has donated its amino acid (p.73)

Question 27

List three possible posttranslational modifications.

Answer 27

1.) Trimming (removal of N or C terminal peptides); 2.) Covalent Alterations (phosphorylation, glycosylation, hydroxylation, methylation, acetylation); 3.) Proteasomal degradation (attachment of ubiquitin to defective proteins to tag them for breakdown) (p.73)