(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
examples of tumour suppressor genes
TP53
BRCA1
BRCA 2
what is required for the development of cancer?
not just one but MULTIPLE DNA mutations
(existing hereditary mutations may then increase your chances of getting cancer)
What is the cause of Huntington’s disease?
the one with the sheep
triplet insertion expansion - adds a bunch of extra codons (CAG)
why does RBC shape matter (eg. in sickle cell disease?)
affects surface area for O2 transport and also movement in blood vessels
sickle shaped may accumulate and cause blockages
