INVESTIGADORES
ANGEL Sergio Oscar
congresos y reuniones científicas
Título:
The histone γH2A.X is involved in Toxoplasma gondii replication-associated DNA stress
Autor/es:
BOGADO SS; DALMASSO MC; VANAGAS L; GANUZA A; FENOY IM; KIM K; SULLIVAN WJ; ANGEL SO
Lugar:
Oxford
Reunión:
Congreso; 12th International Congress on Toxoplasmosis; 2013
Resumen:
Toxoplasma gondii is an apicomplexan parasite with a
complex life cycle composed of multiple stages. The tachyzoite stage, which
occurs in both definitive and intermediate hosts, is a highly replicative phase
that disseminates to almost all tissues and organs. A H2A.X histone was
recently described in the parasite that associates with inactive
chromatin, and its phosphorylated form (γH2A.X) is present at basal levels even
without exogenous DNA damage. H2A.X associates with H2Ba, but not H2Bv (renamed
H2B.Z), the partner of H2A.Z. Ectopic expression of T. gondii H2A.X and
a mutated version that replaced the C-terminal serine 131 (S131) withalanine, both fused to c- myc epitope (mycH2AX and mycH2AXS131A
respectively), showed that the S131 is not required for genome
positioning of this histone in silenced chromatin or for dimerization with
canonical H2B. However S131 is important for normal parasite
replication. This growth impairment increased in the presence of the
topoisomerase I inhibitor camptothecin (CPT). The mycH2AX lines exhibited
resistance to CPT. We also found that the parasites H2A.X is
phosphorylated throughout the cell
cycle, mainly during S phase. Our data suggest that the basal γH2A.X in the tachyzoite could be
associated with replication-associated DNA stress.