3
Isolation of temperature-sensitivemutants in yeast
• Mutants grow normally atpermissive temperature
• Mutants loses genefunction at restrictivetemperature
• Thousands of cell cyclemutants have beenidentified
4
A cell-cycle mutant in yeast
• (a) growth at permissivetemperature displays buds ofall sizes
• (b) growth at restrictivetemperature shows cells havefinished first cell cycle andarrested in the second
Fig. 15.6
8
Three cell cycle check points ensure genomic stability
G1 to S (start) check pointsG2 to M check pointsMetaphase-anaphase check points
10
Interactions between various tumor suppressorsand proto-oncogenes in growth control of a cell
Fig. 15.24
12
-members of Li-Fraumeni cancer-prone families wereshown to carry germ-line p53 mutations.-mice that are homozygous null for p53 are highlypredisposed to tumors.
p53: an anti-oncogenic protein
18
General cancer phenotype includesmany types of cellular abnormalities
• Autocrine stimulation –tumor cells make their ownsignals to divide
• Loss of contact inhibition –lost property to stopdividing when contactedby another cell
• Loss of cell death –resistance to programmedcell death
• Loss of gap junctions – nochannels for connecting toneighbor cell
20
Changes that enable tumor to disrupt localtissue and invade distant tissues
• Ability to metastasize• Angiogenesis – secrete substances that cause blood vessels to grow
toward tumor• Evasion of immune surveillance
21
A. Cancer phenotype results fromaccumulation of multiple mutations in theclonal progeny of cells
B. Most cancers result from exposures tomutagens
• If one sib or twin gets cancer, other usually does not• Populations that migrate – profile of cancer becomes
more like people indigenous to new location
24
Cancer mutations occur in two forms
• Oncogenes– dominant
mutations• Mutant tumor-
suppressor genes– recessive
mutations
26
• Exposure of noncancerouscells to tumor DNA inculture– Human tumor DNA to
transform normal mousecells
– Human DNA isolatedfrom transformants