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

It is seen that frame shift mutations occur in tumor suppressor genes due to the presence of microsatellite mutator region which are simple repeats. These are prone to frame shift mutations because the daughter and template strand may align improperly. Thus, results in extrahelical loops which causes frame shift within the tumor suppressor genes.

Dominant negative mutation is a type of mutation which is antagonistic to the wild type allele.i.e. when present it will lead to negative effects as opposed to the positive effects of the wildtype allele.

p53 is a tumor supressor protein. It causes supression of damaged DNA to enter S-phase. and arrest the cell to repair DNA or the cell it sent for apoptosis.
When mutated to a dominant negative mutation, it will not supress the damaged DNA and allow cell entry into the Sphase replicating the damaged DNA and causing growth and multiplication of cancerous cells.

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