Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program

First human retrovirus discovered, HTLV-1 infects approximately twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most important are the adult T-cell leukemia (ATL) and a neurodegenerative disorder called HAM/TSP (Human associated myelopathy/ Tropical spastic paraparesis). We are interested in the mechanisms of transformation by the viral Tax oncoprotein. Recently, we showed that Tax interacts with the minichromosome maintenance MCM2-7 helicase and binds to origins of DNA replication (Boxus et al, 2012 Blood 119:151). Thereby, Tax modulates the spatiotemporal program of origin activation during the S phase of cell cycle. In fact, Tax accelerates S phase progression by inducing early firing of late replication origins. Concomitantly, Tax-MCM2-7 interplay also modulates viral transcription. Together, our data demonstrates that interaction between Tax and MCM2-7 is involved in replication reprogramming and viral transcription.