Selected topics in molecular biology

Review session Nov. 26, 2007

All nucleotides have a common structure

There are five principal bases in nucleic acids

A, G, T, C are present in DNAA, G, U, C are present in RNA

Inosine is carbonylatedadenosine

UMP

1) Ribonucleotide reductase catalyzes thesynthesis of deoxyribonucleotides

Inhibited by hydroxyurea, which is used as anti-cancer drug

2) Thymidylate synthase catalyzes the methylation of dUTP

Conversion of ribo-to-deoxyribonucleotides

UMP

Anti-cancer drugsspecifically blockdTMP production

Folic acid

Defects in the purine salvage pathway cause human diseases

Salvage PathwayActivated ribose (PRPP) + base

Nucleotides

De Novo PathwayActivated ribose (PRPP) + amino acids

+ ATP + CO2 +……….

Nucleotides

Blocked by HGPRT deficiency (Gout, Lesh-Nyhan)

PRPP

DNA can undergo reversible strand separation

Theeukaryoticreplication fork

Replication protein A

Replicationfactor C

Inhibited by rifamycins(e.g., Rifampicin)

The base pair in the 3rd codon position can “wobble”

frameshift mutations

Exchange of genetic material during meiosis

Recombination=crossover + exchange of DNA betweentwo DNA double strands

Organization and rearrangement of heavy-chain DNA

V=variableD=diversityJ=joiningC=constant

VDJ recombination allows forantibody diversity

Different classes of immunoglobulin (isotypes) fulfill different tasks

major class major class membrane- unknown against In serum in external bound parasites, secretions allergies

1st lineof defense

Cell Cycle Control

Multiple cdks and cyclins regulate passage of mammalian cells through the cell cycle

Restriction point is analogous to START

Cdc2/Cdk1-cyclin BCdc2/Cdk1-cyclin A

Cdk2-cyclin A

Cdk2-cyclin E

Cdk4-cyclin DCdk6-cyclin D

good genes bad genes

proto-oncogenes oncogenesare required for promote uncontollednormal growth growth gain-of-function

mutation (can bepoint mutation, insertion or deletion)

Besides mutations in proto-oncogene/tumor suppressor coding regions, mutationsin gene regulatory elements (promoter) can deregulate the expression pattern

tumor suppressors inactive tumor suppressor

loss-of-functionmutation

Membrane receptorsand signal

transduction cascades

Cell-surface receptors belong to different classes

G protein-coupled receptors contain 7 transmembrane alpha-helices

Acetylcholine receptor in the heart muscle opens K+ channels

frequency of heartcontractions goes down