When oncogenes are activated by mutation we most often find that the mutation is

Question

When oncogenes are activated by mutation we most often find that the mutation is a substitution while when tumor suppressor genes are mutated the common mutation is an insertion/deletion. Why is this? p53 is a tumor suppressor gene yet mutations in p53 found in cancers are more often substitutions not insertion/deletions and these mutations are dominate loss of function as opposed the recessive. We call this type of mutation dominate negative, explain what is meant by that terminology. Explain how the inactivation of p53 is different than other tumor suppressors.

Explanation / Answer

Dominant negative mutation is a type of mutation that negatively affects the function of the wid type gene allele since it is dominant to wild type allele it is called "Dominant negative".

p53 is inactive in normaly dividing cells, it can interact with mdm2 and it is supressed. but when it is mutated, it is unable to siganl detachment from the mdm2 complex. accumulating large amounts of p53 mutated proteins. This protein does not allow cell cycle supression even when DNA damage has occured in the cell cycle.

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