In: Biology
A mutation in the ras cellular oncogene can cause cancer when it is in the heterozygous condition, but a mutation in the RB tumor suppressor gene can cause cancer only when it is in the homozygous condition. What does this difference between dominant and recessive mutations imply about the roles that the ras and RB gene products play in normal cellular activities?
Membrane-associated G proteins (Ras protein are encoded by the ras gene), are involved in activating the signalling cascade and key nuclear genes to regulate the cell cycle. The ras gene is mutated in many cancers.
Point mutations in the coding region or in the controlling sequences (promoter, regulatory elements, enhancers) can change a proto-oncogene into an oncogene by causing an increase in either the activity of the gene product or the expression of the gene, the latter leading in turn to an increase in the amount of gene product. For example, the ras mutations are typically point mutations.
Due to gene amplification of proto-oncogenes, (overreplication of small segments of the genomic DNA) resulting in increased amount of gene product which inturn contribute to unscheduled cell proliferation. For example, multiple copies of ras are found in mouse adrenocortical tumors.
ras is dominant gene its mutation leads to cancer in the heterozygous condition.
The functional Retinoblastoma (RB) (Tumor Suppressor Gene) gene translates to nuclear phosphoprotein (pRB). pRB is involved in regulating the cell cycle at the G1-to-S checkpoint.
RB tumor suppressor gene can cause cancer only when it is in the homozygous condition (recessive gene) because the mutated pRB synthesised is truncated and unstable to activate DNA synthesis genes so lead to cancer formation.