A5005809670- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Cancer therapeutics and mechanisms
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Carcinogens and Genotoxicity Assessment
- Genomics and Chromatin Dynamics
- Metal complexes synthesis and properties
- Metalloenzymes and iron-sulfur proteins
- Bacterial Genetics and Biotechnology
- Peptidase Inhibition and Analysis
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- Microtubule and mitosis dynamics
- Cancer-related gene regulation
- RNA Interference and Gene Delivery
- Polyomavirus and related diseases
- Telomeres, Telomerase, and Senescence
- Mitochondrial Function and Pathology
- Cell death mechanisms and regulation
- Cancer Genomics and Diagnostics
NĒRx BioSciences (United States)
2014-2025
Indiana University School of Medicine
2016-2025
Indiana University – Purdue University Indianapolis
2016-2025
Indiana University
2013-2025
University of Indianapolis
2012-2024
University School
2013-2024
Indiana University Indianapolis
2013-2022
Indiana University Health
2011-2020
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
2020
Palmetto Hematology Oncology
1997-2013
Using purified proteins from calf and a synthetic substrate, we have reconstituted the enzymatic reactions required for mammalian Okazaki fragment processing in vitro. The are removal of initiator RNA, synthesis an upstream to generate nick, then ligation. With our RNase H type I (RNase HI) makes single cut one nucleotide 5' RNA-DNA junction. double strand specific 3' exonuclease removes remaining monoribonucleotide. After dissociation cleaved by DNA polymerase generates which is sealed...
Abstract The combination of cisplatin and ionizing radiation (IR) treatment represents a common modality for treating variety cancers. These two agents provide considerable synergy during treatment, although the mechanism this remains largely undefined. We have investigated sensitization to IR using in vitro vivo experiments. A clear synergistic interaction between is observed cells proficient nonhomologous end joining (NHEJ) catalyzed repair DNA double-strand breaks (DSB). In contrast, no...
In addition to increased DNA-strand exchange, a cytogenetic feature of cells lacking the RecQ-like BLM helicase is tendency for telomeres associate. We also report additional cellular and biochemical evidence role in telomere maintenance. co-localizes complexes with repeat protein TRF2 that employ recombination-mediated mechanism lengthening known as ALT (alternative telomeres). foci actively synthesizing DNA during late S G 2 /M; co-localization increases /M when thought occur....
Translesion synthesis past Pt−DNA adducts can affect both the cytotoxicity and mutagenicity of platinum adducts. We have shown previously that extent replicative bypass in vivo is influenced by carrier ligand The specificity may be determined DNA polymerase complexes catalyze translesion and/or damage-recognition proteins bind to block replication. In present study, primer extension on templates containing site-specifically placed cisplatin, oxaliplatin, JM216, or chlorodiethylenetriamine−Pt...
Abstract Purpose: To investigate SGI-110 as a “chemosensitizer” in ovarian cancer and to assess its effects on tumor suppressor genes (TSG) chemoresponsiveness-associated silenced by DNA methylation cancer. Experimental Design: Several cell lines were used for vitro vivo platinum resensitization studies. Changes expression levels of TSG other cancer-related response measured pyrosequencing RT-PCR. Results: We demonstrate that resensitized range platinum-resistant cells cisplatin (CDDP)...
DNA-dependent protein kinase (DNA-PK) orchestrates DNA repair by regulating access to breaks through autophosphorylations within two clusters of sites (ABCDE and PQR). Blocking ABCDE phosphorylation (by alanine mutation) imparts a dominant negative effect, rendering cells hypersensitive agents that cause double-strand breaks. Here, mutational approach is used address the mechanistic basis this effect. hypersensitizes most types damage (base damage, cross-links, breaks, induced replication...
The catalytic activity of the calf thymus 5'-to 3'-exonuclease was measured on substrates consisting two primers annealed adjacent to each other a template.Exonucleolytic degradation downstream primer is very slow if are separated by gap one nucleotide or no upstream present.When only nick separates primers, rapid.This suggests that nuclease designed work with DNA polymerases such synthesis from an creates favored substrate.Nuclease action then destroys substrate, but it regenerated further...
The heterotrimeric DNA-binding protein, replication protein A (RPA), consists of 70-, 34-, and 14-kDa subunits is involved in maintaining genomic stability by playing key roles DNA replication, repair, recombination. RPA participates these processes through its interaction with other proteins strong affinity for single-stranded (ssDNA). RPA-p34 phosphorylated a cell-cycle-dependent fashion primarily at Ser-29 Ser-23, which are consensus sites Cdc2 cyclin-dependent kinase. By systematically...
Targeting uncontrolled cell proliferation and resistance to DNA-damaging chemotherapeutics with a single agent has significant potential in cancer treatment. Replication protein A (RPA), the eukaryotic ssDNA-binding protein, is essential for genomic maintenance stability via roles both DNA replication repair. We have identified novel small molecule that inhibits vitro cellular activity of RPA, prevents cycle progression, induces cytotoxicity, increases efficacy chemotherapeutic agents. These...
Protein-DNA interactions underpin essential cellular processes. Understanding these is critical for elucidating the molecular mechanisms of various pathways. Key factors such as structure, sequence, and length a DNA molecule can significantly influence protein binding. Bio-layer interferometry (BLI) label-free technique that measures binding kinetics between molecules, offering straightforward precise approach to quantitatively study protein-DNA interactions. A major advantage BLI over...
The Ku70-Ku80 (Ku) heterodimer complex plays a central role in the non-homologous end joining (NHEJ) double-strand break (DSB) repair pathway and DNA damage response (DDR). Like DNA-PK, Ku is promising drug target for cancer treatment when combined with radiotherapy or DSB-inducing agents. We have previously reported first-in-class early-generation highly potent specific Ku-DNA binding inhibitors (Ku-DBi’s) that block interaction inhibit DNA-PK kinase activity. These Ku-DBi’s also cellular...
Replication protein A (RPA) is a heterotrimeric composed of 70-, 34-, and 14-kDa subunits that has been shown to be required for DNA replication, repair, homologous recombination. We have previously preferential binding recombinant human RPA (rhRPA) duplex cisplatin-damaged compared with the control undamaged (Patrick, S. M., Turchi, J. (1998) Biochemistry 37, 8808–8815). Here we assess rhRPA containing site-specific cisplatin-DNA adducts. bind 1.5–2-fold better 30-base pair substrate single...
AbstractDNA mismatch repair (MMR) is a critical genome-stabilization system. However, the molecular mechanism of MMR in human cells remains obscure because many components have not yet been identified. Using functional vitro reconstitution system, this study identified three HeLa cell fractions essential for MMR. These divide into two distinct stages: mismatch-provoked excision and synthesis. In dissection reaction crucial intermediates elucidated biochemical functions individual hitherto...