In a recent study of CRC samples, 39% were found to be KRAS mutated and 8% of mutations were located in codon 61 (Sundstrom et al, 2010).
Subsequent sequencing of the products revealed that all these alleles were either doubly mutated or wild type, indicating that, in every case, both mutations were located on the same allele.
Five (of six) missense mutations were located in the kinase domain of BUBR1.
Interestingly, the RNA sequencing data also revealed a survival/proliferation-associated signature in the flow-sorted cells in which the mutations were located.
In addition, several required mutations were located outside the ligand binding pocket and yet exerted important action on ligand binding.
Amino acid sequence analysis indicated that the most of the mutations were located on the enzyme surface.
These mutations were located almost in all regions of the mitochondrial genome, including the regions coding 3 complexes (Complex I, Complex IV and Complex V), 4 tRNAs and 2 rRNAs.
Our results explain why certain pRNA mutants are inactive in DNA packaging while remaining competent in procapsid binding, since the mutations were located in a domain involved in DNA translocation that is dispensable for procapsid binding.
All of these mutations were located in a region encoding the Helicase C domain, which is involved in regulating gene transcription.
Surprisingly, all the suppressive mutations were located nearby yvbK like sup8 (linkage of 60 90%).
All mutations were located in exon 10, only synonymous substitutions were detected in exon 2, irrespectively of the health status.
