Deciphering the insights of poly(ADP-ribosylation) in tumor progression.

Poly (ADP-ribose) polymerase (PARP) inhibitors are particularly efficient against tumors with defects in the homologous recombination repair pathway. Nonetheless poly(ADP-ribosylation) (PARylation) modulates prometastasic activities and adaptation of tumor to a hostile microenvironment. Modulation of metastasis-promoting traits is possible through the alteration of key transcription factors involved in the regulation of the hypoxic response, the recruitment of new vessels (or angiogenesis), and the stimulation of epithelial to mesenchymal transition (EMT).

ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy.

In response to nutrient stress, cells start an autophagy program that can lead to adaptation or death. The mechanisms underlying the signaling from starvation to the initiation of autophagy are not fully understood. In the current study we show that the absence or inactivation of PARP-1 strongly delays starvation-induced autophagy.

Radiation induced apoptosis and initial DNA damage are inversely related in locally advanced breast cancer patients.

Background: DNA-damage assays, quantifying the initial number of DNA double-strand breaks induced by radiation, have been proposed as a predictive test for radiation-induced toxicity. Determination of radiation-induced apoptosis in peripheral blood lymphocytes by flow cytometry analysis has also been proposed as an approach for predicting normal tissue responses following radiotherapy. The aim of the present study was to explore the association between initial DNA damage, estimated by the number of double-strand breaks induced by a given radiation dose, and the radio-induced apoptosis rates observed.

PARP inhibitors: new partners in the therapy of cancer and inflammatory diseases.

Poly(ADP-ribose) polymerases (PARPs) are defined as cell signaling enzymes that catalyze the transfer of ADP-ribose units from NAD(+) to a number of acceptor proteins. PARP-1, the best characterized member of the PARP family, which currently comprises 18 members, is an abundant nuclear enzyme implicated in cellular responses to DNA injury provoked by genotoxic stress. PARP is involved in DNA repair and transcriptional regulation and is now recognized as a key regulator of cell survival and cell death as well as a master component of a number of transcription factors involved in tumor development and inflammation.

PARP-1 is involved in autophagy induced by DNA damage.

Autophagy is a lysosome-dependent degradative pathway frequently activated in tumor cells treated with chemotherapy or radiation. PARP-1 has been implicated in different pathways leading to cell death and its inhibition potentiates chemotherapy-induced cell death. Whether PARP-1 participates in the cell's decision to commit to autophagy following DNA damage is still not known.

Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition.

ATM and PARP-1 are two of the most important players in the cell's response to DNA damage. PARP-1 and ATM recognize and bound to both single and double strand DNA breaks in response to different triggers. Here we report that ATM and PARP-1 form a molecular complex in vivo in undamaged cells and this association increases after gamma-irradiation.

PARP-1 modifies the effectiveness of p53-mediated DNA damage response.

The tumour suppressor protein p53 plays a key role in the cell's decision to arrest the cell cycle or undergo apoptosis following a genotoxic insult. p53 is stabilized and activated after DNA damage, however the cascade of events signalling from DNA lesions to p53 stabilization and activation is still controversial. Poly (ADP-ribosylation) of different nuclear acceptors by PARP-1 is an early event when a single strand DNA lesion is produced.