(02) Mutation and Cancer Flashcards
consequences of DNA alteration on germ cells vs somatic cells
alterations to germ line passed on to future progeny
somatic / local has more local effects (Eg. tumour)
two types of DNA alterations
large scale = chromosomal rearrangements
small scale = one / few nucleotides altered
two types of small scale mutations
substitutions
Insertions / deletions (Indels)
substitutions can be:
silent
missense
nonsense
indels can cause
Frameshifts (1n, 2n, 3n)
what is a silent mutation?
DNA has a change, but it does NOT change the amino acid it codes for, so no impact on the protein
describe a missense mutation
a nucleotide pair substitution codes a different protein - effect depends on what the amino acid did originally
describe a nonsense mutation
single base substitution causes a STOP codon
causes a TRUNCATED PROTEIN
what are the “Stop” codons?
UAA
UAG
what are the consequences of deletions
causes a frameshift, downstream residues, protein completely altered
what type of mutation causes sickle cell anaemia?
missense substitution
beta-globin DNA, mRNA reads GUG instead of GAG and codes for Val rather than Glu
What is cyclin?
regulates the cell cycle
a protein that fluctuates throughout the cell cycle - low during G1 / S, increases through G2 and steep drop during M
it activates cyclin-dependent kinase
what is Maturation (or M-phase) promoting factor?
MPF
a specific type of cyclin + cyclin-dependent kinase complex that is KEY FOR G2 CHECKPOINT
what is the function of MPF
Maturation/M-phase promoting factor is responsible for the phosphorylation of many other proteins, ALLOWING MITOSIS TO COMMENCE
(concentration high during M phase)
how do cell signals work at checkpoints
generally STOP / GO molecules
STOP genes keep proliferation in check
GO genes stimulate cell proliferation
how do tumours arise?
DNA mutations change functions of STOP / GO molecules
cell cycle proceeds when STOP /GO molecules are not functioning correctly –> uncontrolled cell growth
–> tumour
how do cancer-causing DNA mutations arise?
Genetic predisposition (inherited from parents, all cells of body)
Acquired (local, one cell initially - UV damage, smoking, carcinogens etc)
what are proto-oncogenes?
genes that stimulate cell proliferation
proto = has the potential to be an oncogene, a cancer cell (-onco)
what are tumor suppressor genes?
genes that normally keep proliferation in check
how do alterations in proto-oncogenes and/or tumour suppressor genes cause uncontrolled cell growth?
over-activation of proto-oncogenes
deactivation of tumour suppressor genes
describe a normal cell-stimulating pathway
a LIGAND BINDS TO A RECEPTOR, causing the activation of the protein kinase cascade, and transcription factors in nucleus, so a protein that stimulates the cell cycle is produced
describe a mutant cell cycle-stimulating pathway (increased function) with examples
even in the absence of a ligand in the receptor, G protein (eg. Ras, a GTPase) + protein kinases and transcription factors (eg. Myc) may always be active, hence overexpression of protein and increased cell division
two examples of proto-oncogenes
Ras - a GTPase
Myc - a transcription factor
describe a normal cell-cycle inhibiting pathway vs a mutant pathway
DNA damage in genome activates protein kinases –> active form of p53 –> transcription –> protein that inhibits cell cycle
in mutant path, defective / missing transcription factor, inhibitory protein not produced
