PT  - JOURNAL ARTICLE
AU  - Katerina Leonova
AU  - Alfiya Safina
AU  - Elimelech Nesher
AU  - Poorva Sandlesh
AU  - Rachel Pratt
AU  - Catherine Burkhart
AU  - Britney Lipchick
AU  - Costakis Frangou
AU  - Igor Koman
AU  - Jianmin Wang
AU  - Kirill Kirsanov
AU  - Marianna G. Yakubovskaya
AU  - Andrei V. Gudkov
AU  - Katerina Gurova
TI  - TRAIN in response to treatment with anti-cancer small molecule destabilizing chromatin
AID  - 10.1101/142471
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 142471
4099  - http://biorxiv.org/content/early/2017/05/25/142471.short
4100  - http://biorxiv.org/content/early/2017/05/25/142471.full
AB  - Genome stability is in the focus of research for many decades, while stability and integrity of chromatin is far less studied. Cell identity in multicellular organism is completely dependent on chromatin stability, therefore there should be mechanisms ensuring maintenance of epigenetic integrity. Previously, we have found that loss of DNA methylation in the absence of p53 leads to the transcription of silenced repetitive elements, such as pericentromeric repeats and endogenous viruses, what causes activation of IFN response, similarly to viral invasion, and IFN-dependent cell death. We named this phenomenon TRAIN (Transcription of Repeats Activates INterferon). Now we found that small molecule, curaxin, which destabilizes nucleosome via binding to DNA and deforming helix shape, causes TRAIN independently on p53 status. Curaxin demonstrated activity as cancer treatment and preventive agent via established previously p53 activating and NF-kappaB inhibiting activities. Here we showed that activation of IFN response is an additional mechanism of inhibition of oncogene-induced transformation by curaxin. Our data suggest that TRAIN is a response to the loss of chromatin stability and one of the mechanisms which prevents oncogene-induced transformation.