A5033993667- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- PARP inhibition in cancer therapy
- DNA and Nucleic Acid Chemistry
- Genomics, phytochemicals, and oxidative stress
- Advanced biosensing and bioanalysis techniques
- Nuclear Structure and Function
- Microtubule and mitosis dynamics
- RNA Interference and Gene Delivery
- Carcinogens and Genotoxicity Assessment
- Cell death mechanisms and regulation
- Polyomavirus and related diseases
- Cancer therapeutics and mechanisms
- Acute Lymphoblastic Leukemia research
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- Neurogenetic and Muscular Disorders Research
Institute of Genetics
2011-2024
HUN-REN Szegedi Biológiai Kutatóközpont
2012-2024
Masaryk University
2011-2016
Hungarian Academy of Sciences
2006-2016
St. Anne's University Hospital Brno
2013
University Hospital Brno
2013
Brigham and Women's Hospital
2012
University of Szeged
2005
DNA damage, such as abasic sites and strand breaks with 3′-phosphate 3′-phosphoglycolate termini present cytotoxic mutagenic threats to the cell. Class II AP endonucleases play a major role in repair of well 3′-modified termini. Human cells contain two class endonucleases, Ape1 Ape2 proteins. possesses strong AP-endonuclease activity weak 3′-phosphodiesterase 3′–5′ exonuclease activities, it is considered be endonuclease human cells. Much less known about Ape2, but its importance emphasized...
DNA double-strand breaks (DSBs) can be generated not only by reactive agents but also as a result of replication fork collapse at unrepaired lesions. Whereas ubiquitylation proliferating cell nuclear antigen (PCNA) facilitates damage bypass, modification yeast PCNA small ubiquitin-like modifier (SUMO) controls recombination providing access for the Srs2 helicase to disrupt Rad51 nucleoprotein filaments. However, in human cells, roles SUMOylation have been explored. Here, we characterize SUMO...
Unrepaired DNA damage may arrest ongoing replication forks, potentially resulting in fork collapse, increased mutagenesis and genomic instability. Replication through lesions depends on mono- polyubiquitylation of proliferating cell nuclear antigen (PCNA), which enable translesion synthesis (TLS) template switching, respectively. A proper rescue is ensured by the dynamic ubiquitylation deubiquitylation PCNA; however, as yet, little known about its regulation. Here, we show that human...
Homologous recombination (HR) is essential for maintaining genomic integrity, which challenged by a wide variety of potentially lethal DNA lesions. Regardless the damage type, known to proceed RAD51-mediated D-loop formation, followed repair synthesis. Nevertheless, participating polymerases and extension mechanism are not well characterized. Here, we present reconstitution this step using purified human proteins. In addition Pol δ, TLS polymerases, including η κ, also can extend D-loops....
The addition of poly(ADP-ribose) (PAR) chains along the chromatin fiber due to PARP1 activity regulates recruitment multiple factors sites DNA damage. In this manuscript, we investigated how, besides direct binding PAR, early unfolding events controlled by PAR signaling contribute lesions. We observed that different DNA-binding, but not histone-binding, domains accumulate at damaged in a PAR-dependent manner, and correlates with their affinity for DNA. Our findings indicate is promoted...
The error-free repair of double-strand DNA breaks by homologous recombination (HR) ensures genomic stability using undamaged sequence to copy genetic information. While some the aspects initial steps HR are understood, molecular mechanisms underlying events downstream D-loop formation remain unclear. Therefore, we have reconstituted D-loop-based in vitro recombination-associated synthesis assay and tested efficacy polymerases Pol δ η extend invaded primer, ability three helicases (Mph1, Srs2...
Human Ape2 protein has 3' phosphodiesterase activity for processing 3'-damaged DNA termini, 3'-5' exonuclease that supports removal of mismatched nucleotides from the 3'-end DNA, and a somewhat weak AP-endonuclease activity. However, very little is known about role in repair processes. Here, we examine effect interaction with proliferating cell nuclear antigen (PCNA) on its enzymatic activities targeting to oxidative lesions. We show PCNA strongly stimulates Ape2, but no Moreover, find upon...
Stalling of replication forks at unrepaired DNA lesions can result in discontinuities opposite the damage newly synthesized strand. Translesion synthesis or facilitating copy from strand sister duplex by template switching overcome such discontinuities. During switch, a new primer–template junction has to be formed and two mechanisms, including fork reversal D-loop formation have been suggested. Genetic evidence indicates major role for yeast Rad5 switch that both its human orthologue,...
Successful and accurate completion of the replication damage-containing DNA requires mainly recombination RAD18-dependent damage tolerance pathways. RAD18 governs at least two distinct mechanisms: translesion synthesis (TLS) template switching (TS)-dependent Whereas TS is error-free, TLS can work in an error-prone manner and, as such, regulation these pathways tight control to prevent errors potentially oncogenic transformation tumorigenesis. In humans, PCNA-associated inhibitor (PARI)...
Switching between replicative and translesion synthesis (TLS) DNA polymerases are crucial events for the completion of genomic when replication machinery encounters lesions in template.In eukaryotes, translesional polymerase (Pol) plays a central role accurate bypass cyclobutane pyrimidine dimers, predominant induced by ultraviolet irradiation.Pol deficiency is responsible variant form Xeroderma pigmentosum (XPV) syndrome, characterized predisposition to skin cancer.Here, we show that FF...
Abstract Genome replication is frequently impeded by highly stable DNA secondary structures, including G-quadruplex (G4) DNA, that can hinder the progression of fork. Human WRNIP1 (Werner helicase Interacting Protein 1) associates with various components machinery and plays a crucial role in genome maintenance processes. However, its detailed function still not fully understood. Here we show human interacts G4 structures provide evidence for contribution to processing. The absence results...
The integrity of the genetic material is crucial for every organism. One intrinsic attack to genome stability stalling replication fork which can result in DNA breakage. Several factors, such as lesions or formation stable secondary structures (eg, G-quadruplexes) lead stalling. G-quadruplexes (G4s) are well-characterized that form within specific single-stranded sequence motifs and have been shown block/pause machinery. In most genomes several helicases described regulate G4 unfolding...