Reference : Reprogramming of replication origin firing and checkpoint adaptation in adult T cell ...
Scientific congresses and symposiums : Unpublished conference/Abstract
Human health sciences : Oncology
http://hdl.handle.net/2268/138998
Reprogramming of replication origin firing and checkpoint adaptation in adult T cell leukemia
English
Barez, Pierre-Yves mailto [Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc. >]
Carpentier, Alexandre mailto [Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc. >]
Willems, Luc mailto [Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc. >]
14-Dec-2012
No
National
GIGA-Cancer Seminar
14 Décembre 2012
Université de Liège - Ecole Doctorale Thématique en Cancérologie Expérimentale & GIGA Cancer
Liège
Belgique
[en] Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most common are the adult T-cell leukemia (ATL) and a neurodegenerative disorder called HAM/TSP (Human associated myelopathy/ Tropical spastic paraparesis). A key parameter of HTLV-1 pathogenesis is faster replication of provirus-carrying lymphocytes allowing clonal expansion of infected cell populations. The virally-encoded Tax oncoprotein plays an essential role in this process by interacting with DNA replication origins and accelerating S phase progression. By reprogramming the timing of origin firing, Tax also creates a replicative stress leading to DNA double strand breaks. This mechanism further triggers the DNA damage response (DDR) that induces cell cycle arrest and initiates either apoptosis or senescence. However, HTLV-1 infected cells have developed strategies to interfere with the DDR and are adapted to checkpoint control. These cells are thus able to proliferate despite occurrence of DNA damage. Based on these observations, we now propose a novel therapeutic approach based on the principle of synthetic lethality.
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/138998

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