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Interaction of HTLV-­1 Tax with minichromosome maintenance proteins accelerates the replication timing program
Carpentier, Alexandre; Barez, Pierre-Yves; Willems, Luc
2013GIGA Day 2013
 

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Keywords :
HTLV-1; Tax; MCM2-7; Replication timing; DNA Damage Response (DDR); Genomic Stress
Abstract :
[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.
Disciplines :
Oncology
Author, co-author :
Carpentier, Alexandre ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Barez, Pierre-Yves ;  Université de Liège - ULiège > Doct. sc. agro. & ingé. biol.
Willems, Luc  ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Language :
English
Title :
Interaction of HTLV-­1 Tax with minichromosome maintenance proteins accelerates the replication timing program
Publication date :
28 January 2013
Event name :
GIGA Day 2013
Event place :
Liège, Belgium
Event date :
28 Janvier 2013
Available on ORBi :
since 16 January 2013

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