Endogeneous DNA double strand breaks in the human and murine MLL gene

The human MLL gene is recurrently involved in chromosomal translocations with a large variety of different translocation partner genes. Recent studies have identified two recombination clusters where chromosomal translocations map in the breakpoint cluster region of the human MLL gene. Interestingly, one of these hot spot coincides with chromosomal breakpoints that can be exogenously induced by the application of several substances, including epipodophyllotoxins (VP16 or VM26) or by simply inducing apoptosis.

Here we present data about where these DNA double strand breaks occur in the human MLL gene when treated with Topo I and Topo II inhibitors. DNA double strand breaks on two non-homologous chromosome are the prerequisite that leads to chromosomal translocations. We also present preliminary data of the murine system which suggests that transcriptional processes – and not the inhibition of topoisomerase II – may be responsible for the observed DNA strand breaks in the MLL gene.

Supported by grant KR-S07T04 from the NGFN.