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NBME 22 Answers

nbme22/Block 2/Question#35

A 45-year-old man with Li-Fraumeni syndrome agrees ...

Decreased binding of RNA polymerase

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 +21  upvote downvote
submitted by seagull(467),

Did anyone need to read that last sentence like 50 times because the author refuses to use better grammar. Just frustrating.

link981  Author rationale: "What is grammar?" +2  




 +3  upvote downvote
submitted by yotsubato(309),

p53 is mutated and cant bind the TATA box, so what happens to transcription of inhibitory proteins?

Is basically what this question is trying to ask...

So no TATA box promoter => Decreased binding of RNA polymerase

link981  You said it, they are "trying" to ask. Should use better grammar. +1  
titanesxvi  This is on first aid, and says that the promoter region is where RNApolymerase binds +  




For this one I think what you had to know is that Transcription (DNA-->RNA) is performed by RNA polymerase. It was not DNA polymerase because this one replicates (DNA-->DNA)

fenestrated  between increased or decreased binding I picked decreased because it was a mutation which affected the hydrogen bonds which is how nucleotides bind to each other +  




 +2  upvote downvote
submitted by d_holles(41),

This is a good picture of an experiment showing this:

https://www.nature.com/articles/1210296/figures/1

Oncogene volume 26, pages 2212–2219 (2007)





 +0  upvote downvote
submitted by pipter(4),

Does anyone have any specific idea on the mechanism of the p53 mutation question regarding the TATA box (the one with the single amino acid conversion and the different hydrogen bonding)?

I chose the decreased binding of RNA polymerase on the TATA sequence of genes that inhibit cell division based solely on the fact that p53 is a tumor suppressor (aka mutated p53->less inhibition of division->multiple divisions).

joha961  From a random paper I found, “Arguably p53’s most important function is to act as a transcription factor that directly regulates perhaps several hundred of the cell’s RNA polymerase II (RNAP II)-transcribed genes.” So normally it increases RNA pol binding; a mutation would decrease it. +  
estsosa  The TATA box is part of the promoter region site where RNA polymerase II and other transcription factors bind to DNA. A defect would therefore decrease binding of RNA polymerase. +4  
mnemonia  Also you can reason it out (I got this wrong because you have to be really meticulous) since we know that loss of p53 = cancer. Cancer = want more cell division = don’t want inhibitory gene = less transcription of said gene. +  




Why is this not increased binding of DNA polymerase?

This mutation should cause cellular division ie DNA replication and cause increased binding to origin replication sequences ie TATA by DNA polymerase.

brise  It's talking about mutations on the transcription of genes that inhibit the cell division. Also RNA polymerase binds to the promoter region. +  
nwinkelmann  Also, the question specifically (though in a very wordy, convoluted way) asked what the effect of the mutation on transcription was. DNA pol is not used in transcription, it is used in replication. RNA pol is used in transcription. In terms of increased or decreased binding, argining is polar/positively charged and proline is neutral/nonpolar, so there are fewer H-bonding sites, and thus decreased binding of the RNA pol. +1  
medn00b  Could this convoluted question also mean.......... that since the gene to make p53 is messed up due to the hydrogen bonds, RNA polymerase will not be able to bind to make the mRNA ... So there will be cancer? Because P53 is a tumor suppressor... lemme know thanks guys +  




 +0  upvote downvote
submitted by hello(79),

The grammar of the actual Q was confusing.

To make better sense, it should say "Which of the following is the most likely result on the transcription of genes that inhibit cell division and that contain the consensus sequeence TATA..."

So, the Q is asking about the tp53 gene and specifically about the tp53 gene promoter region.

Promoter regions have a TATA box (obviously, meaning rich in A-T base pairs). A-T base pairing has 2 hydrogen bonds, which makes them easier to cleave --> allows for DNA transcription to occur more easily. RNA Pol does transcription of DNA into RNA.

The entire Q-stem talks about how Li-Fraumeni is due to a mutation in tp53 gene, leading to a lack of tumor suppression activity.

So, if the promoter region TATA box of the tp53 gene is mutated, then the tp53 gene will not get transcribed --> this is why there will be decreased RNA Pol binding. RNA Pol will have a reduced ability to bind tp53 --> less tumor supressor gene transcription --> less tumor suppression.