Friday, May 3, 2013

DISRUPTION AT BRCA IS TRULY BAD FOR OUR PATIENTS!

Before we start this discussion, let's remind ourselves what we know about the BRCAs by taking the example of BRCA-1
"
BRCA1 is expressed in the cells of breast and other tissue, where it helps repair damaged DNA, or destroy cells if DNA cannot be repaired. If BRCA1 itself is damaged, damaged DNA is not repaired properly and this increases risks for cancers (see BRCA mutation).[7][8]
The protein encoded by the BRCA1 gene combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC).[9] The BRCA1 protein associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. Thus, this protein plays a role in transcription, DNA repair of double-stranded breaks[8] ubiquitination, transcriptional regulation as well as other functions.[10]"wikipedia

This statement is a global description of many bad thing this BRCA does to people who have it. 

And until this is re-emphasized, one may not know the full extent of the danger lurking in BRCA positive patients! 
BRCA is not just a mere a DNA repair gene.  And cells have all kind of gene repair genes,  BRCA is also primarily a tumor suppression gene, in its wilde type it is attached to COBRA1, a true COBRA with its eyes on several bad genes that encode proteins which the cell wanted to keep in check.  These molecules are known as NEGATIVE ELONGATIONS PROTEINS.  And there is a number of them, and each once uncontrolled due to mutation of the BRCA gene will go to induce unduly other deleterious consequences...
Let's take the COBRA-1 itself, once unable to tie itself to the mutated BRCA, it will unnecessarily stimulate the Estrogen receptor alpha, and will reach at this area even the stress pathway c-JUN, and c-fos  triggering manufacturing of unnecssary cyclins and growth factors, or the stuff that worsen cancers!

But we can choose to look at ARAF, another elongation proteins which, by being part of the RAF, will amplify the MAPK kinase pathway, this effect is seen even into the Mitochondria (waking the MTOR up )

if you pick the RDBP elongation factor, it will do what negative elongation factor generally do which is to amplify RNA polymerase and ready it to induce DNA polymerase for cell proliferation by DNA multiplicaton

the TH1L, will impact the DSIF and exacerbate RDBP actions!

You see that a good wild BRCA suppresses all these activities by elongation proteins, while repairing DNA mistakes.

I SHOULD EMPHASIZE THAT THE MOST IMPORTANT TARGET IN THIS TRACK IS THE RNA POLYMERASE THAT EVERY SINGLE NEGATIVE ELONGATION MOLECULE WANTS SO BADLY TO AMPLIFY!  IT HAS DOMINION OVER DNA POLYMERASE IN THIS CASE!

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