A5073517046- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Integrated Circuits and Semiconductor Failure Analysis
- RNA and protein synthesis mechanisms
- Toxin Mechanisms and Immunotoxins
- RNA Research and Splicing
- Plant Genetic and Mutation Studies
- Electrostatic Discharge in Electronics
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Genomics and Chromatin Dynamics
- Calcium signaling and nucleotide metabolism
- Force Microscopy Techniques and Applications
- RNA Interference and Gene Delivery
- Genetic Neurodegenerative Diseases
- Pharmacological Effects of Natural Compounds
- DNA and Nucleic Acid Chemistry
- Molecular Biology Techniques and Applications
- Cell death mechanisms and regulation
- Sirtuins and Resveratrol in Medicine
- Mitochondrial Function and Pathology
- Genomics and Phylogenetic Studies
- Ion-surface interactions and analysis
- RNA modifications and cancer
- Advanced Electron Microscopy Techniques and Applications
Institute of Chemical Biology and Fundamental Medicine
2016-2025
Siberian Branch of the Russian Academy of Sciences
2016-2025
Russian Academy of Sciences
2014-2024
Novosibirsk State University
2019-2023
The capacity of human poly(ADP-ribose) polymerase-1 (PARP-1) to interact with intact apurinic/apyrimidinic (AP) sites in DNA has been demonstrated. In cell extracts, sodium borohydride reduction the PARP-1/AP site complex resulted covalent cross-linking PARP-1 DNA; identity cross-linked was confirmed by mass spectrometry. Using purified PARP-1, specificity binding AP site-containing competition experiments. only weakly activated conduct synthesis upon DNA, but strongly for strand incision...
Poly(ADP-ribose) polymerases (PARPs/ARTDs) use nicotinamide adenine dinucleotide (NAD+) to catalyse the synthesis of a long branched poly(ADP-ribose) polymer (PAR) attached acceptor amino acid residues nuclear proteins. PARPs act on single- and double-stranded DNA breaks by recruiting repair factors. Here, in vitro biochemical experiments, we found that mammalian PARP1 PARP2 proteins can directly ADP-ribosylate termini oligonucleotides. preferentially catalysed covalent attachment ADP-ribose...
PARP1 and PARP2 are implicated in the synthesis of poly(ADP-ribose) (PAR) after detection DNA damage. The specificity interaction with long fragments containing single- and/or double-strand breaks (SSBs DSBs) have been studied using atomic force microscopy (AFM) imaging combination biochemical approaches. Our data show that localizes mainly on exhibits a slight preference for nicks over DSBs, although protein has moderately high affinity undamaged DNA. In contrast to PARP1, is detected at...
Poly(ADP-ribose) polymerases (PARPs) act as DNA break sensors and catalyze the synthesis of polymers ADP-ribose (PAR) covalently attached to acceptor proteins at damage sites. It has been demonstrated that both mammalian PARP1 PARP2 PARylate double-strand termini in oligonucleotide duplexes vitro. Here, we show PARP3 can mono(ADP-ribosyl)ate (MARylate), respectively, 5'- 3'-terminal phosphate residues double- single-strand a molecule containing multiple strand breaks. PARP3-catalyzed...
Naked mole rat (NMR) is the long-lived and tumor-resistant rodent. NMRs possess multiple adaptations that may contribute to longevity cancer-resistance. However, whether have more efficient DNA repair not been directly tested. Here we compared base excision (BER) nucleotide (NER) systems in extracts from NMR mouse fibroblasts after UVC irradiation. Transcript levels of key enzymes demonstrated most cases higher inducibility vs cells. Ratios activities somewhat varied depending on...
The regulation of repair processes including base excision (BER) in the presence DNA damage is implemented by a cellular signal: poly(ADP-ribosyl)ation (PARylation), which catalysed PARP1 and PARP2. Despite ample studies, it far from clear how BER regulated PARPs roles are distributed between PARPs. Here, we investigated effects PARP1, PARP2 PARylation on activities main enzymes (APE1, polymerase β [Polβ] ligase IIIα [LigIIIα]) combination with scaffold protein XRCC1 nucleosomal context. We...
The maintenance of genome stability and the prevention genotoxic damage to DNA require immediate repair. In cell, repair process is usually preceded by a release from complexes with chromatin proteins accompanied nucleosome sliding, relaxing or disassembly. Base excision (BER) corrects most common lesions, which does not disturb helix dramatically. Notably, small lesions can be repaired in without global decompaction. One regulatory mechanisms poly(ADP-ribosyl)ation, leading relaxation...
ABSTRACT Poly(ADP-ribose) polymerases are critical enzymes contributing to regulation of numerous cellular processes, including DNA repair. Within the PARP family, PARP1 and PARP2 primarily facilitate PARylation in nucleus, particularly responding genotoxic stress. The activity PARPs is influenced by nature damage multiple protein partners, with HPF1 being important one. Forming a joint active site (PARP2), contributes histone following chromatin remodelling during stress events. This study...
7-Methylguanine (7-MG), a natural compound that inhibits DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1), can be considered as potential anticancer drug candidate. Here we describe study of 7-MG inhibition mechanism using molecular dynamics, fluorescence anisotropy and single-particle Förster resonance energy transfer (spFRET) microscopy approaches to elucidate intermolecular interactions between 7-MG, PARP-1 nucleosomal DNA. It is shown competes with substrate NAD+ its binding in...
Y-box-binding protein 1 (YB-1) is a multifunctional positively charged that interacts with DNA or RNA and poly(ADP-ribose) (PAR). YB-1 poly(ADP-ribosyl)ated stimulates polymerase (PARP1) activity. Here, we studied the mechanism of YB-1-dependent PAR synthesis by PARP1 in vitro using biochemical atomic force microscopy assays. activity known to be facilitated co-factors such as Mg2+. However, contrast an Mg2+-dependent reaction, activation accompanied overall up-regulation PARylation...
Abstract Poly(ADP-ribosyl)ation catalyzed by poly(ADP-ribose) polymerases (PARPs) is one of the immediate cellular responses to DNA damage. The histone PARylation factor 1 (HPF1) discovered recently form a joint active site with PARP1 and PARP2 was shown limit activity PARPs stimulate their NAD + -hydrolase activity. Here we demonstrate that HPF1 can DNA-dependent DNA-independent autoPARylation as well heteroPARylation histones in complex nucleosome. stimulatory action detected defined range...
Poly(ADP-ribose) polymerase 2 (PARP2) participates in base excision repair (BER) alongside PARP1, but its functions are still under study. Here, we characterize binding affinities of PARP2 for other BER proteins (PARP1, APE1, Polβ, and XRCC1) oligomerization states the homo- hetero-associated complexes using fluorescence-based light scattering techniques. To compare PARP1 efficiency PAR synthesis, absence presence protein partners, size PARylated various reaction conditions was measured....
We report on the design, synthesis and molecular modeling study of conjugates adenosine diphosphate (ADP) morpholino nucleosides as potential selective inhibitors poly(ADP-ribose)polymerases-1, 2 3. Sixteen dinucleoside pyrophosphates containing natural heterocyclic bases well 5-haloganeted pyrimidines, mimicking a main substrate these enzymes, nicotinamide adenine dinucleotide (NAD+)-molecule, have been synthesized in high yield. Morpholino tethered to β-phosphate ADP via phosphoester...
DNA repair capacity in cells of naked mole rat (Hgl), a species known for its longevity and resistance to cancer, is still poorly characterized.Here, using the whole-cell extracts (WCEs) Hgl, mouse human cells, we studied interrelation between synthesis on substrates base excision activity poly(ADP-ribose) polymerases (PARPs) responsible transfer ADP-ribose moieties onto different targets.The level PAR was more than ten-fold higher WCE as compared rodent WCEs, while efficiency...
Genome compaction is one of the important subject areas for understanding mechanisms regulating genes' expression and DNA replication repair. The basic unit in eukaryotic cell nucleosome. main chromatin proteins responsible have already been identified, but regulation architecture still extensively studied. Several authors shown an interaction ARTD with nucleosomes proposed that there are changes nucleosomes' structure as a result. In family, only PARP1, PARP2, PARP3 participate damage...