L25 Tumour suppressor genes Flashcards
Tumour suppressor genes
control cell cycle
loss of activity => uncontrolled cell division
p53
Oncogenes
promote cell division
overactive => uncontrolled division
myc gene
Mutations can lead to cancer
need balance between p53 and myc, balance between tumour suppression and cell division genes
overexpression of myc oncogene
causes tumours in fish
Mitogen - myc - retinoblastoma
see onenote
mitogen stimulates cell cycle entry
DNA damage - p53
see onenote slides
p53 blocks cell cycle if myc is overactive
=> cell cycle arrest or apoptosis
p53 phosphorylated => becomes active
p53 activates p21 gene
p21 is a CKI
Multiple avenues to inactivating the second allele of TP53
therefore factors/accidents decreasing precision of cell cycle increase chance of inactivating function
Peto’s paradox
risk of developing cancer should theoretically increase with both the number of cells and the lifespan of an organism
BUT humans with more cells than mice, live longer
cancer is not the major cause of mortality for large and long-lived wild animals despite increased theoretical risks
Peto’s paradox - one solution?
African elephants contain 40 copies of the p53 genes
extra copies of p53 gene may enable elephants to kill off potentially cancerous cells before they form tumours
Peto’s paradox - one solution?
African elephants contain 40 copies of the p53 genes
extra copies of p53 gene may enable elephants to kill off potentially cancerous cells before they form tumours
Cancer
caused by mutations that may be inherited, induced by environmental factors or result from DNA replication errors (R)
found that R mutations responsible for 2/3 of mutations in human cancers
Naked mole rats
defy biological law of ageing
- rarely get cancer, resistant to some types of pain, can survive up to 18 minutes without oxygen
- risk of death doesn’t go up as they grow older
- very active DNA repair and high levels of chaperones