C to T Transition Mechanism

Question

[L. A. Liggett]

I am seeing C to T transitions in my sequencing data, but also some strange signatures that follow along with that. I am trying to understand the biology of what is occurring. In the data I see more C to T changes than G to A changes, when it would be expected that these numbers would be relatively the same.

So, in-vivo when a C to T transition occurs, does the complementary base get changed to ensure watson and crick binding, or will you end up with a T-G pair? This would explain the phenomenon that I am seeing but I don't know if this happens. (Andy references would also be super helpful. Thanks.)

[natasha.sernova]

See these articles:.

http://www.ncbi.nlm.nih.gov.sci-hub.cc/pubmed/20920744#

DNA Methylation and Cancer

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978439/

Cancer mutation signatures, DNA damage mechanisms, and potential clinical implications

Wiki:

https://en.wikipedia.org/wiki/Transition_(genetics)

https://en.wikipedia.org/wiki/CpG_site#CpG_islands

"How methylation of CpG sites followed by spontaneous deamination leads to a lack of CpG sites in methylated DNA. As a result, residual CpG islands are created in areas where methylation is rare, and CpG sites stick (or where C to T mutation is highly detrimental)."

[L. A. Liggett]

@natasha.sernova Am I missing the answer to my question here? I don't think any of these solve my problem.

Answer 1

[WouterDeCoster]

I hope my molecular understanding isn't too degraded and I don't make capital mistakes, here we go:

The biology behind the C to T transitions (if I understand your question correctly) is oxidative deamination. If you google 'oxidative deamination cytosine' you'll get plenty of hits, but I can already give you this: http://www.pnas.org/content/95/7/3578.full (I haven't read the paper but sounds like something interesting for you).

Regarding your second question: the complementary base will not change, a single mismatch in a long sequence is not a real problem. The error might get corrected by mismatch repair enzymes in the cell, but if not it can persist. The real trouble arises during replication, in which one daughter molecule will keep the 'correct' nucleotide and as such remain normal, but the other will inherit the faulty nucleotide and will get a complementary base for that one, after which no repair is possible.

You are vague considering 'the phenomenon you see' and 'some strange signatures' so can't really help with that unless you have more information!

[L. A. Liggett]

@WouterDeCoster So this is exactly what I am talking about. I suspected that the complementary base would not be changed upon deamination of a cytosine, but I have had trouble finding any references that show this. Do you know of any?

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