A5062033577- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Toxin Mechanisms and Immunotoxins
- Cell death mechanisms and regulation
- CRISPR and Genetic Engineering
- Calcium signaling and nucleotide metabolism
- Integrated Circuits and Semiconductor Failure Analysis
- Plant Genetic and Mutation Studies
- Microtubule and mitosis dynamics
- Autophagy in Disease and Therapy
- Cancer-related Molecular Pathways
- Sirtuins and Resveratrol in Medicine
- Telomeres, Telomerase, and Senescence
- Electrostatic Discharge in Electronics
- Mitochondrial Function and Pathology
- Carcinogens and Genotoxicity Assessment
- Pancreatic function and diabetes
- Cancer, Hypoxia, and Metabolism
- Diet and metabolism studies
- Low-power high-performance VLSI design
- Nuclear Structure and Function
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Healthcare Systems and Challenges
- Rice Cultivation and Yield Improvement
Université de Strasbourg
2016-2025
International Drug Development
2024
Institut Polytechnique de Bordeaux
2024
Biotechnologie et Signalisation Cellulaire
2014-2023
Centre National de la Recherche Scientifique
2013-2022
École Supérieure de Biotechnologie de Strasbourg
2011-2022
Institut de génétique et de biologie moléculaire et cellulaire
2021
École Normale Supérieure - PSL
2003-2017
VA National Center of Oncology after Fanarjyan
2011
University of Miami Health System
2011
In mammalian cells, damaged bases in DNA are corrected by the base excision repair pathway which is divided into two distinct pathways depending on length of resynthesized patch, replacement one nucleotide for short-patch repair, and resynthesis several nucleotides long-patch repair. The involvement poly(ADP-ribose) polymerase-1 (PARP-1) both has been investigated using PARP-1-deficient cell extracts to single abasic sites derived from uracil or 8-oxoguanine located a double-stranded...
Mitochondrial disorders are highly heterogeneous conditions characterized by defects of the mitochondrial respiratory chain. Pharmacological activation biogenesis has been proposed as an effective means to correct biochemical and ameliorate clinical phenotype in these severely disabling, often fatal, disorders. Pathways related targets Sirtuin1, a NAD+-dependent protein deacetylase. As NAD+ boosts activity Sirtuin1 other sirtuins, intracellular levels play key role homeostatic control...
The ADP ribosyl transferase [poly(ADP-ribose) polymerase] ARTD3(PARP3) is a newly characterized member of the ARTD(PARP) family that catalyzes reaction ribosylation, key posttranslational modification proteins involved in different signaling pathways from DNA damage to energy metabolism and organismal memory. This enzyme shares high structural similarities with repair enzymes PARP1 PARP2 accordingly has been found catalyse poly(ADP ribose) synthesis. However, relatively little known about...
ADP‐ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage viral infection is involved intra‐ extracellular signaling, chromatin transcriptional regulation, protein biosynthesis, cell death. ADP‐ribosylation catalyzed ADP‐ribosyltransferases (ARTs), which transfer ADP‐ribose from NAD + onto substrates. The modification, occurs as mono‐ or poly‐ADP‐ribosylation, reversible due...
AbstractCell survival after genotoxic stress is determined by a counterbalance of pro- andanti-death factors. Sirtuins (SIRTs) are deacetylases that promote cell whereaspoly(ADP-ribose) polymerases (PARPs) can act both as and death inducingfactor the two protein families strictly dependent on NAD+ for their activities.Here we report SIRT1 modulates PARP-1 activity upon DNA damage. Activation ofSIRT1 resveratrol leads to reduced there drastic increase inPAR synthesis in sirt1-null cells. The...
The DNA damage-dependent poly(ADP-ribose) polymerase-2 (PARP-2) is, together with PARP-1, an active player of the base excision repair process, thus defining its key role in genome surveillance and protection. Telomeres are specialized DNA-protein structures that protect chromosome ends from being recognized processed as strand breaks. In mammals, telomere protection depends on T2AG3 repeat binding protein TRF2, which has been shown to remodel telomeres into large duplex loops (t-loops)....
Immunoglobulin class switch recombination (CSR) is initiated by DNA breaks triggered activation-induced cytidine deaminase (AID). These activate damage response proteins to promote appropriate repair and long-range recombination. Aberrant processing of these breaks, however, results in decreased CSR and/or increased frequency illegitimate between the immunoglobulin heavy chain locus oncogenes like c-myc. Here, we have examined contribution sensors Parp1 Parp2 resolution AID-induced during...
Poly(ADP-ribosyl)ation (PARylation) is a posttranslational modification involved in multiple biological processes, including DNA damage repair. This catalyzed by poly(ADP-ribose) polymerase (PARP) family of enzymes. PARylation composed both linear and branched polymers (PAR). However, the biochemical mechanism polymerization functions PAR chains are elusive. Here we show that PARP2 preferentially activated subsequently catalyzes chain synthesis. Notably, direct binding to N-terminus promotes...
Significance Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA repair protein and part of the genome maintenance network. On other hand, PARP-1 involved in pathophysiological processes such as inflammation. Chronic inflammation has emerged key event carcinogenesis, including formation colorectal cancer (CRC). Our data reveal that abundantly expressed human CRC, correlating with disease progression. Using transgenic mouse models, we show fosters inflammation-driven tumor growth stimulates...
Poly(ADP-ribose) polymerase (PARP) is an element of the DNA damage surveillance network evolved by eukaryotic cells to cope with numerous environmental and endogenous genotoxic agents. PARP has been found be involved in vivo both cell proliferation base excision repair DNA. In this study interaction between alpha-primase tetramer examined. We provide evidence that proliferating cells: (i) physically associated catalytic subunit tetramer, association confirmed confocal microscopy,...
We present the first evidence for a fast activation of nuclear protein poly(ADP-ribose) polymerase (PARP) by signals evoked in cell membrane, constituting novel mode signaling to nucleus. PARP, an abundant, highly conserved, chromatin-bound found only eukaryotes, exclusively catalyzes polyADP-ribosylation DNA-binding proteins, thereby modulating their activity. Activation reportedly induced formation DNA breaks, is involved transcription, replication, and repair. Our findings demonstrate...
Besides the established central role of poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 in maintenance genomic integrity, accumulating evidence indicates that poly(ADP-ribosyl)ation may modulate epigenetic modifications under physiological conditions. Here, we provide vivo for pleiotropic involvement both meiotic postmeiotic processes. We show Parp-2-deficient mice exhibit severely impaired spermatogenesis, with a defect prophase meiosis I characterized by massive apoptosis at pachytene...
Poly(ADP-ribosyl)ation is a post-translational modification of proteins involved in the regulation chromatin structure, DNA metabolism, cell division and death. Through hydrolysis poly(ADP-ribose) (PAR), Poly(ADP-ribose) glycohydrolase (PARG) has crucial role control life-and-death balance following insult. Comprehension PARG function been hindered by existence many isoforms encoded single gene displaying various subcellular localizations. To gain insight into response to irradiation, we...
Poly(ADP-ribose)polymerase 1 (PARP1) is well characterized for its role in base excision repair (BER), where it activated by and binds to DNA breaks catalyzes the poly(ADP-ribosyl)ation of several substrates involved damage repair. Here we demonstrate that PARP1 associates with telomere repeat binding factor 2 (TRF2) capable TRF2, which affects TRF2 telomeric DNA. Immunostaining interphase cells or metaphase spreads shows detected sporadically at normal telomeres, but appears preferentially...