So, I have read quite a lot of papers that have studied the structure of DNMT3A and its mechanism; however, I couldn't really understand the mechanism fully. Hopefully, you guys can help me understand :)
Based on what I have read, DNMT3A works as a heterotetramer (DNMT3L-DNMT3A-DNMT3A-DNMT3L). Also, based on two papers published in Nature by J. Song and X. Cheng, the two DNMT3A active sites target CpG sites that are separated by approximately 10 to 14 base pairs apart.
So for example, if the DNA sequence is
_________1__________________2_________
5'-CATGCGTTCTAATTAGAACGCATG-3' (sense strand)
3'-GTACGCAAGATTAATCTTGCGTAC-5' (antisense strand)
One of DNMT3A active site will methylate CG (1) and the other DNMT3A active site will methylate CG (2).
Now my question is whether this DNMT3A methylates only the sense strand CG or only the antisense strand CG or both.
Also, if only one of my DNMT3A has a mutation which results in inactive form of DNMT3A (meaning formation of DNMT3L-inactive DNMT3A - active DNMT3A- DNMT3L), what will happen?
Should I expect either CG (1) or CG (2) methylated but not both?
Those are great questions. I have not worked enough in this area to definitively give you an answer. I would recommend that you directly contact the PI of the recent structural paper you cited, and ask them. I am guessing that they will appreciate your interest. Good luck.
Dear Jihoon Han;
For the first question, I think both strands would be methylated.
For the second question, only the mutated version would not be inactivated that is bound to other inactivated points i.e. not both sites.
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