DNA methylation

[Monique]

I heard that a methylated cytosine converts into a thymine by the following mechanism:


The metC during the replication of DNA is place w/ an A opposite, and after the second replication you get what looks like a C to T transition.


But isn't the metC to T transition caused by the de-amination of the metC?

[Another God]

I have just been studying DNA repair mechanisms in E. Coli, and what I got out of that was that after replication of DNA, over a period of time, all of the A's get methylated, and that is all. I got the impression that C's, G's and T's are never methylated. Maybe I only got that impression though because I am only looking at one area. Biochemistry likes to make lots of different situations where things go differently.

Does this sound like I might have anything useful to offer? Or am I completely off the track u are interested in?

(I am quite up to date now on Photoreactivation repair, Excision repair, Recombination Repair and SOS repair...)

[Another God]

Oh yeah, I get what u mean now. U are saying that the methylation occurs on the 5-Carbon of C, and somewhere in the reaction, the Amine group is lost, resulting in a chemical change from C to T (rather than an actual base change where the C gets detached, and a T get attached.)

well, it seems possible (I know nothing about it directly)

2 thoughts:

First: Perhaps this occurance gives the average cell a good evolutionary reason to onyl Methylate Adenines...?

Second: Why is the A placed opposite the C in the first place? Is that just an error? And if that was to even happen, I can't see how the H binding interaction between an A and a C would cause the C to deaminate. Unless this is catalysed by some enzyme (a strange thing to be catalysed), it seems like a strange sort of random mutation to occur.

[iansmith]

Hi

Monique, it appears that you are that both explanations your given are the same but there seen to be missing information to the first explanation. Here how i learned in my advance genetic classes:

C spontaneoulsy deaminates to at a frequency of 10 ^-3 and it is normally repaired by Uracil DNA glycosylase (UDG). The problem is if C is methyated then 5-methyl U = T. UDG cannot repair the this because t is a normal DNA base pair. This mismatch appear on the mother/methylated strand and an A is inserted to the daughter/unmethylated strand. Ttherefore C is match with an A.

Another god your partly right about the A methylation. Methylation in E. coli occurs at a high frequency at A residues but still occurs on G, C and T but at very low frequency.

Also, even though association of the C and A does not make sense, DNA polymerase is not perfect and will mismatch base pair at a frequency ranging form 10^-6 to 10^-9. these mismatch can be repair by using enzyme that have for reference the mother/methylated strand. Also keep in mind that if DNA polymerase would be perfect there would be no mutation and no evolution.


Ian

[Monique]

Thank you both, that clears things up. Ian: may I ask about your background?

[iansmith]

I have a B. Sc in microbiology my undergrad project was to sequence a plasmid from H. ovis and i am starting my master in microbiology and have to sequence the hemoglobin receptor gene and study how H. ovis acquires Iron from hemoglobin.

[Monique]

Cool, so you are going to mutate the receptor? Btw, what is H. Ovis? A common bacteria?

[iansmith]

We migth knock out the Hm receptor if i have time. Histophilus ovis is not a common bacteria, it is member of the pasteurellaceae ( Hemophilus influenzae for example) and it is a sheep pathogen. Not much people are studying this bacteria.

[Monique]

Originally posted by iansmith
Not much people are studying this bacteria. So why are you interested in it?

[iansmith]

Working with bacteria that are not common makes your research more interresting because everythings you do is pretty much new. I also took the project my supervisor gave me and i don't why he was interested by this bacteria.