ИСТИНА

Erroneous repair of DNA double strand breaks (DSBs) sometimes leads to chromosomal translocations associated with carcinogenesis. Translocation partners often belong to different chromosomes, therefore spatial mobility of the certain loci in nucleus plays the crucial role in the processes of these translocations. Using 3D-FISH and other approaches it has been shown that HIV-encoded Tat protein rapidly activates transcription of the nuclease-encoding RAG1 gene. This created DSBs in the MYC gene locus which then moved towards the center of the nucleus where it sustainably colocalized with IGH. Spatial proximity increase probability of the t(8;14) chromosomal translocation which takes place at Burkitt lymphoma. We create a cell line to observe dynamic of the certain DNA loci in a living cell. For this purpose, we use ANCHOR system which is a bipartite system composed of ANCH sequences and OR proteins. ANCH DNA sequences inserted in studied locus are specifically and independently recognized by OR proteins that nucleate and spread from the ANCH sequence over surrounding DNA. As the OR proteins fused to a fluorescent reporter, increased concentration of OR on the ANCH DNA creates a fluorescent focus detectable by fluorescence microscopy. We have already generated cell line with ANCH integrated in MYC locus and with ОR-GFP. Investigation of MYC and IGH movement will help develop new therapeutic attitudes can be envisioned to prevent lymphomas in high-risk groups