A5036981751- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Integrated Circuits and Semiconductor Failure Analysis
- Toxin Mechanisms and Immunotoxins
- Electrostatic Discharge in Electronics
- Genomics and Chromatin Dynamics
- Calcium signaling and nucleotide metabolism
- Plant Genetic and Mutation Studies
- CRISPR and Genetic Engineering
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Environmental and Biological Research in Conflict Zones
- Silk-based biomaterials and applications
- Plant Reproductive Biology
- Biochemical and Structural Characterization
- Advanced biosensing and bioanalysis techniques
Institute of Chemical Biology and Fundamental Medicine
2018-2025
Siberian Branch of the Russian Academy of Sciences
2018-2024
Russian Academy of Sciences
2023
Novosibirsk State University
2018-2022
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...
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...
Y-box-binding protein 1 (YB-1) is a multifunctional cellular factor overexpressed in tumors resistant to chemotherapy. An intrinsically disordered structure together with high positive charge peculiar YB-1 allows this function almost all events related nucleic acids including RNA, DNA and poly(ADP-ribose) (PAR). In the present study we show that acts as potent polymerase (PARP1) cofactor can reduce efficiency of PARP1 inhibitors. Similarly histones or polyamines, stimulatory effect on...
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...
Y-box-binding protein 1 (YB-1) is a multifunctional involved in the regulation of gene expression. Recent studies showed that addition to its role RNA and DNA metabolism, YB-1 PARP1 activity, which catalyzes poly(ADP-ribose) [PAR] synthesis under genotoxic stress through auto-poly(ADP-ribosyl)ation or trans-poly(ADP-ribosyl)ation. Nonetheless, exact mechanism by regulates PAR remains be determined. contains disordered Ala/Pro-rich N-terminal domain, cold shock an intrinsically C-terminal...
Nucleosome core particles (NCPs) are basic units of chromatin organization; they represent the most convenient model system for study key DNA-dependent processes.Therefore, a robust method nucleosome assembly is important research.To prepare NCPs, purified histones and DNAs with sequences providing strong positioning DNA relative to histone octamer commonly used, control efficacy NCP reconstruction required.Aim.To optimize procedure reconstitution from octamers different types synthetic...
Poly(ADP-ribose) (PAR) is a negatively charged polymer, linear and branched, consisting of ADP-ribose monomers. This polymer synthesized by poly(ADP-ribose)polymerase (PARP) enzymes which are activated on DNA damage use nicotinamide adenine dinucleotide (NAD+) as substrate. The most studied members the PARP family, PARP1 PARP2, important nuclear proteins involved in many cellular processes, including regulation repair. PARP2 catalyze both synthesis transfer poly(ADP-ribose) to amino acid...
ABSTRACT The repair processes regulation including base excision (BER) is implemented by a cellular signal PARylation catalysed PARP1 and PARP2. Despite intensive studies, it far from clear how BER regulated PARPs the roles are distributed between PARPs. Here, we investigated effects of PARP1, PARP2 on activities main enzymes (APE1, Polβ LigIIIα) in combination with XRCC1 nucleosomal context. We constructed nucleosomes midward- or outward-oriented damage. It was concluded that most cases,...