Gene Transcription & Cancer Pathways Flashcards
Describe the genetic code
defines the relationship between;
- the sequence of bases in the DNA
- the sequence of amino acids
What are the 3 stages of Transcription?
- Initiation
- Elongation
- Termination
Describe Initiation (1st step of transcription)
- RNA polyermase together transcription factors bind to promoter DNA
- RNAP creates transcritption bubbles, separating the 2 strands of DNA helix
- 6 general transcription factors
What are the 6 general transcription factors ?
TFIIA
TFIIB
TFIID
TFIIE
TFIIF
TFIIH
Describe Elongation (2nd step of transcription)
- RNAP adds RNA nucleotides
- RNA sugar-phosphate backbone forms with assistance from RNAP
What does RNAP stand for ?
RNA Polymerase
What is the rate of elongation in prokaryotes & eukaryotes ?
10-100 nts/sec
Describe Termination (3rd step of transcription)
- hydrogen bonds of RNA - DNA helix breaks & frees newly synthesised RNA strand
- RNA may be further processed
- RNA may remain in nucleus or exit into cytoplasm
Briefly describe translation
- mRNA translated into protein
- more complex than replication or transcription
- takes place on ribosomes
- each codon has its own tRNA
- 3 steps
What are the 3 steps of Translation?
- Initiation
- Elongation
- Termination
Describe the structure of a ribosome?
- binding site for mRNA
- 3 binding sites for tRNA = A & P sites + E site
Describe A & P sites on a ribosome
- aminoacyl & peptidyl sites
- cavities on ribosome where charged tRNA molecules bind during peptide synthesis
Describe initiation (1st step of Translation)
- initiated by a special Met-tRNAi, coded by Aug
- 40S subunit with Met-tRNAi, attaches to 5’ cap, scans mRNA for start codon
- eukaryotic initiation factors (eIF) involved
Describe Eukaryotic Initation Factors
- eIF
- interacts with the 40S ribosomal subunit to stimulate assembly of the translation initiation complex
Describe the Termination (3rd step of translation)
- stop codon triggering release of the completed polypeptide chain - UAG, UAA, UGA
- no tRNA exists for stop codon
- requires specific protein: releasing factor (eRF)
What are some pathways for a normal mammalian cell?
- enter cell cycle & proliferate
- enter G0 quiescence
- commit apoptosis
- change function/differentiate
What are the 4 basic signalling pathways ?
- Enzyme coupled receptors
- G-protein coupled receptors
- Ligan-gated ion channels
- Steroid hormone signalling
Why do mutations occur ?
- cells continuously exposed to DNA damaging events
- 1/2 mutations daily = 10,000 over lifetime
What is the cancer genomic landscape?
- whole genom sequencing comparison of DNA from tumour & tissue
- identify groups of ‘cancer genes’
What 3 categories does loss of control mechanisms mainly occur?
- proto-oncogenes
- tumour suppressor genes
- DNA repair enzymes
Describe how tumour suppressor gene mutations occur?
- 1st mutation = inactivates tumor suppressor genes - no effect in mutation in 1 copy of gene
- 2nd mutation event = inactivates 2nd gene copy
- 2 inactivating mutations eliminate the tumour suppressor gene, promoting cell transformation
What are some hallmarks of cancer?
- inducing angiogenesis
- resisting cell death
- evading growth supressors
