Cancer genes Flashcards
Describe DNA damage repair genes
Repair mechanism fro DNA (point mutations etc.)
Both (pair) fail for cancer to arise
Speeds accumulation of mutations in other critical genes
Describe tumour suppressor genes
Inhibit cell cycle or promote apoptosis (self destruct)
Like breaks - both fail for cancer (one autosomal dominant/ environmental)
1st mutation - susceptible to cancer
2nd mutation - leads to cancer
Describe the importance of BRAC1
Check point mediator DNA damage signalling + repair Chromatin remodelling (inactive X)
Describe BRAC2
DNA repair by homologous recombination
Breast and ovarian cancer 50 - 85%
Describe the function MMR
Corrects errors that spontaneously occur during DNA replication (insertion/deletion)
Describe Microsatellite instability (MSI)
Phenotypic evidence that MMR isn’t functioning properly
Abnormal MMRs accumulates errors, increasing the chances of cancer
What properties doc cancer cells have?
Loss of tumour suppressor genes
Gain of function of oncogenes
Abnormal shape/size
Capable of independent growth
What facilitates the movement of a tumour
The loss of cell-to-cell adhesion
What are the main mutations in cancer
Mutations at G1 and S by;
Rb, CDK4, cyclin D, p16
What active enzyme complex is the main checkpoint in cancer
CDK/ cyclin complex
What is a cyclin
regulatory subunit
What are cyclin- dependent kinases
catalytic subunit
continuously expressed in inactive form - activated by cyclins
What does the CDK/cyclin complex do?
phosphorylate target proteins which activate the substrate to regulate the next phase
What does p53 maintain?
genomic integrity
What does p53 do in damaged cells?
Induces cell cycle arrest at G1
Facilitates DNA repair
Describe p53 induced apoptosis in damaged cells
Cells with mutated p53 don’t G1 arrest or repair DNA so proliferate to form a malignant tumour
What does E2F do
protein that binds to DNA and stimulates cell to divide
What binds to E2F to make it inactive
Rb gene
What happens to the Rb gene once it is phosphorylated
Can no longer bind to E2F
What are proto-oncogenes
Normal genes that promote normal cell growth and mitosis
What do tumour suppressor genes regulate? (anti- oncogenes)
apoptosis and DNA repair
How are oncogenes activated
Mutation occurs
dysregulation of proto-oncogene
Turns to oncogene
CAUSE CANCER
Describe the Go phase of the cell cycle
Resting phase - cell has left cycle and stopped dividing
What 3 phases make up the interphase of the cell cycle?
G1, S, G2