Question

1a. Many uridine molecules are inserted into some mitochondrial mRNAs in trypanosomes.  The uridine residues come from the poly(U) tail of a donor strand!  Nucleoside triphosphates do not participate in this reaction.  Propose a reaction mechanism that accounts for these findings.  (HINT:  relate this RNA editing to RNA splicing.)

b. Analysis of  p53 gene mutations in human tumors shows that a large proportion of these mutations involve GC→AT transitions originating at sites of DNA methylation.  Propose a model to explain preferential mutagenesis of this type at these sites.

Answer 1

1a. Editing in RNA transcript that encode proteins in the mitochondria of trypanosomes. In this case multiple Us are inserted or deleted.

b. Human tumors of different tissue origin display a different nature of inactivating mutation. Close to 50% of all colon cancer bear mutation at the three CpG hot spot codons 175, 248 and 273 of p53 gene. They are G to A transition, thus implicating an endogenous methylation driven process (most probably deamination of 5-methylcytosine; 5 - mc) as a major causative factor.