ABSTRACT
BACKGROUND: Poly(ADP-ribosyl)ation (PARylation), a posttranslational modification introduced by PARP-1 and PARP-2, has first been implicated in DNA demethylation due to its role in base excision repair. Recent evidence indicates a direct influence of PARP-dependent PARylation on TET enzymes which catalyse hydroxymethylation of DNA-the first step in DNA demethylation. However, the exact nature of influence that PARylation exerts on TET activity is still ambiguous. In our recent study, we have observed a negative influence of PARP-1 on local TET-mediated DNA demethylation of a single gene and in this study, we further explore PARP-TET interplay. RESULTS: Expanding on our previous work, we show that both TET1 and TET2 can be in vitro PARylated by PARP-1 and PARP-2 enzymes and that TET1 PARylation negatively affects the TET1 catalytic activity in vitro. Furthermore, we show that PARylation inhibits TET-mediated DNA demethylation at the global genome level in cellulo. CONCLUSIONS: According to our findings, PARP inhibition can positively influence TET activity and therefore affect global levels of DNA methylation and hydroxymethylation. This gives a strong rationale for future examination of PARP inhibitors' potential use in the therapy of cancers characterised by loss of 5-hydroxymethylcytosine.
Subject(s)
Poly ADP Ribosylation , Poly(ADP-ribose) Polymerase Inhibitors , DNA/metabolism , DNA Methylation , DNA Repair , Poly(ADP-ribose) Polymerase Inhibitors/pharmacologyABSTRACT
A gestacao e um periodo de grandes mudancas na vida da mulher. Quando a ele se associa uma patologia, os conflitos existentes tendem a se acentuar. Nesta gestacao, denominada de alto risco, sentimentos como censura, culpa e medo costumam aparecer com frequencia...
Subject(s)
Humans , Female , Adolescent , Adult , Patient Care Team , Pregnancy, High-Risk/psychology , HospitalizationABSTRACT
This study described a modification of a standard method for evaluating the retention and stability of complete denture prostheses. The upper ranges of the Kapur Scale for retention and stability were expanded to improve the sensitivity of this procedure. The standard and modified Kapur scales were also compared with a model using two denture adhesives that have demonstrated varying efficacies when evaluated by more refined laboratory instrumentation. This study verified that the modified Kapur scale was more capable of discriminating the effectiveness between the two denture adhesives, confirming the elevated sensitivity of the modified scale. This improvement of the Kapur scale could be valuable in conducting clinical efficacy trials of denture adhesives when more advanced methodologies present logistic problems.
