Establishment and functional validation of a structural homology model for human DNA methyltransferase 1

Changes in DNA methylation patterns play an important role in tumorigenesis. The DNA methyltransferase 1 (DNMT1) protein represents a major DNA methyltransferase activity in human cells and is therefore a prominent target for experimental cancer therapies. However, there are only few available inhibitors and their high toxicity and low specificity have so far precluded their broad use in chemotherapy. Based on the strong conservation of catalytic DNA methyltransferase domains we have used a homology modeling approach to determine the three-dimensional structure of the DNMT1 catalytic domain. Our results suggest an overall structural conservation with other DNA methyltransferases but also in…

The current progress in sequencing projects calls for rapid, reliable and accurate function assignments of gene products. A variety of methods has been designed to annotate sequences on a large scale. However, these methods can either only be applied for specific subsets, or their results are not formalised, or they do not provide precise confidence estimates for their predictions. We have developed a large-scale annotation system that tackles all of these shortcomings. In our approach, annotation was provided through Gene Ontology terms by applying multiple Support Vector Machines (SVM) for the classification of correct and false predictions. The general performance of the system was bench…