4, 5.1 DNA Repair In Cancer, centrosomes and cancer Flashcards
How is the mitotic spindle useful in cancer treatment?
- The microtubules is targeted
- Stop them from growing so cannot capture chromosomes and align in the middle
- So no division
What is tumour heterogeneity?
- A tumour does not have a single form of genetic disorder
- Multiple variants of cancer cells
- Arises from chromosomal instability
What could be a cause of chromosome instability?
Wrong number of centromeres would lead to multiple spindles
Normal - bipolar
Abnormal - multipolar
Cancer cells have evolved to cluster centrosomes in two areas (centrosome coupling). How can we target this with treatment?
Stop cancer cells clustering
Cell will divide into many, many bits
Too small too survive so die/senescence
What is senescence?
Permanent cell cycle arrest (cells cease to divide)
What is Base Excision Repair?
Base cut out by enzymes
DNA polymerase and ligament replaces it with correct base
What is mismatch repair?
A few nucleotides (200) including strand, removed
Replaced by DNA pol, DNA ligase
What is nucleotide excision repair
Chunk of nucleotides cut out, replaced by DNA pol and DNA ligase
What is a double strand break repair?
Literally 2 ends joined
Easiest way to fix but may cause problems as can lose bases if breaks arent clean
What is intra-tumour-heterogeneity?
Different sub clones in same tumour
Subclone - different group of mutated cells
How is intra tumour heterogeneity a problem to cancer therapy?
One sub clone may be resistant to therapy
Chemo could induce further mutations due to stress
How do cancer therapy agents work? Give an example.
Causing DNA damage
- Strand breaks by radiation
- Cross links
- DNA alkylation
E.g. Camptothecin (chemo)
