Where are replication errors more common/fatal?

[axp107]

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DNA or mRNA...

I remember reading something about one of them having a self-correction mechanism while the other doesn't.

So in which one(s) are replication errors more common? what about more fatal?

 

[themule]

DNA polymerase (DNA==>DNA) has various different proofreading mechanisms. RNA polymerase (DNA==>RNA) apparently has proofreading ability as well but is more error prone that DNAPol. I reading error would, depending on the location, be more problematic with DNAPol as that would affect all proteins transcribed from the area where the error occurs. While a reading error by RNAPol would create a set of bad proteins for the 1/2 life of the mRNA.

TM

 

[kstreet]

My gut tells me DNA has a repair mechanism.
I'm somewhat certain that mutations occur more often in transcription/translation rather than replication.

Best bet is to look it up though.

 

[corbis11]

I believe insertions/deltions that aren't multiples of 3 are the worse since they move the whole reading frame...they aren't the most common if my memory recalls correctly.

DNA would be worse since an mRNA that has an incorrect sequence wont usually fold into its correct 3D conformation = nonfunctional

 

[Funky]

of course problems with DNA are more fatal. Cells may make many mRNA for one gene so if one specific mRNA doesn't work, then you just get a bad protein and the cell will eventually transcript another mRNA anyway. But if you make an error replicating DNA, you'll just never be able to make that protein for that cell. I pity that cell if it replicates more bad cells.

 

[themule]

of course problems with DNA are more fatal. Cells may make many mRNA for one gene so if one specific mRNA doesn't work, then you just get a bad protein and the cell will eventually transcript another mRNA anyway. But if you make an error replicating DNA, you'll just never be able to make that protein for that cell. I pity that cell if it replicates more bad cells.

This is how a lot of cancers pop up. A cells machinery for contact inhibition and also apoptosis are compromised and the cell grows and grows and multiplies and you have tumors.

TM

 

[punkindrublic]

DNA or mRNA...

I remember reading something about one of them having a self-correction mechanism while the other doesn't.

So in which one(s) are replication errors more common? what about more fatal?

DNA has a self-correction mechanism; I believe methyl groups are added to a replicated and error checked strand so when one of the DNA polymerase (I think it's II, but I'm not sure) goes over it for error checking, it knows which is the original and which is replicated. If there's a mismatch, the non-methylated base will be changed. Since RNA is single-stranded, this mechanism obviously can't exist.

As for fatal, I could see that in some cases, it could go either way, but my gut would say in a question like that, it would absolutely be DNA. Remember RNA is non-replicating (comes from DNA) and is eventually degraded and destroyed in the cytoplasm. So unless it codes for a protein that targets something very specifically and resists degradation, it shouldn't have too much of an effect.

So: more common: mRNA, more dangerous: DNA.

 

[Funky]

This is how a lot of cancers pop up. A cells machinery for contact inhibition and also apoptosis are compromised and the cell grows and grows and multiplies and you have tumors.

TM

yes, a mutation in p53 can lead to cancer.

 

[axp107]

of course problems with DNA are more fatal. Cells may make many mRNA for one gene so if one specific mRNA doesn't work, then you just get a bad protein and the cell will eventually transcript another mRNA anyway. But if you make an error replicating DNA, you'll just never be able to make that protein for that cell. I pity that cell if it replicates more bad cells.

Thats what I was thinking... just needed confirmation. 1 DNA can make many mRNAs... but if its faulty, all proteins produced can be faulty. But, if mRNA has errors only 1 protein out of a zillion will be affected.

 

[themule]

yes, a mutation in p53 can lead to cancer.

Not just p53 but also mutations causing constitutive activation of kinases can also cause cancer.

TM

 

[themule]

DNA has a self-correction mechanism; I believe methyl groups are added to a replicated and error checked strand so when one of the DNA polymerase (I think it's II, but I'm not sure) goes over it for error checking, it knows which is the original and which is replicated. If there's a mismatch, the non-methylated base will be changed. Since RNA is single-stranded, this mechanism obviously can't exist.

As for fatal, I could see that in some cases, it could go either way, but my gut would say in a question like that, it would absolutely be DNA. Remember RNA is non-replicating (comes from DNA) and is eventually degraded and destroyed in the cytoplasm. So unless it codes for a protein that targets something very specifically and resists degradation, it shouldn't have too much of an effect.

So: more common: mRNA, more dangerous: DNA.

Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10400-5. Epub 2007 Jun 6.
Selectivity and proofreading both contribute significantly to the fidelity of RNA polymerase III transcription

RNA Pol III has proofreading ability that increases its fidelity by 10^3.

TM

 

[WonderBoy]

DNA or mRNA...

I remember reading something about one of them having a self-correction mechanism while the other doesn't.

So in which one(s) are replication errors more common? what about more fatal?

Errors are more common in mRNA, but that's not a big deal since it doesn't last that long and doesn't get passed down to offspring. DNA has error correcting mechanism during replication.

Nonsense mutation, one that leads to a stop codon, is the worst type of error.

 

[themule]

Errors are more common in mRNA, but that's not a big deal since it doesn't last that long and doesn't get passed down to offspring. DNA has error correcting mechanism during replication.

Nonsense mutation, one that leads to a stop codon, is the worst type of error.

Any mutation that results in early termination would be the worst type of mutation and this can occur through nonsense mutation and frameshift. I think that the one of the key points to remember here is that the genetic code is degenerate do to this it is harder to get a point mutation that results in an AA change. Particularly in the 3rd position.

TM