L11 - Mutations And Cancer Flashcards
Mutations
- Responsible for diversity of genes found among organisms
- can have major, minor, positive or no effects on resulting protein structure and function
Mutation locations
In body: - germ line: passed on - local/somatic: not whole body In DNA: - protein-coding region - introns - 5’/3’ UTR
Types of mutations
- large scale alterations: chromosomal rearrangements
- small scale alterations: one or few nucleotides
Types of small scale alterations
Substitution, indels
Types of substitution mutation
Silent, mis-sense, nonsense
Indels - 1 or 2 nts
Causes frameshift
Could lead to truncated protein
Truncated protein
Shortened protein due to premature STOP codon
Indels - 3 nt-pair
Maintained frameshift
Wild-type beta-globin
5’ GAG 3’
- Glu - (acidic, -ve charge)
Normal hemoglobin
RBC: maximise surface area, flexible - can squeeze through tiny capillaries
Sickle-cell beta-globin
5’ GUG 3’
- Val - (hydrophobic)
Sickle-cell hemoglobin
RBC is more rigid - can get clogged more easily in capillaries
Sickle cell anaemia
- Missense substitution mutation
- result of accumulative effect: needs to happen to enough hemoglobins in RBC
Importance of checkpoints
Appropriate molecular regulation of cell division critical for normal growth, development and maintenance
Maturation promoting factor (MPF) function
phosphorylates many other proteins and allows mitosis to commence
Maturation promoting factor (MPF) composition
Specific complex of cyclin and cyclin dependent kinase (CDK)
Cyclin
- Protein fluctuating throughout cell cycle
- Many different forms - e.g cyclin D, E, A, B