A5009785229- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Carcinogens and Genotoxicity Assessment
- Epigenetics and DNA Methylation
- Mycotoxins in Agriculture and Food
- Advanced biosensing and bioanalysis techniques
- Metal complexes synthesis and properties
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Genomics, phytochemicals, and oxidative stress
- Glutathione Transferases and Polymorphisms
- Molecular Biology Techniques and Applications
- Plant Disease Resistance and Genetics
- RNA and protein synthesis mechanisms
- Cancer therapeutics and mechanisms
- Synthesis and Biological Evaluation
- RNA Interference and Gene Delivery
- Bacterial Genetics and Biotechnology
- Water Treatment and Disinfection
- Cancer Genomics and Diagnostics
- Estrogen and related hormone effects
- Plant Genetic and Mutation Studies
- Genomics and Chromatin Dynamics
Center for Environmental Health
2016-2025
Massachusetts Institute of Technology
2016-2025
IIT@MIT
2017
University of Wisconsin–Madison
2014
Biological E (India)
2011
Northeastern University
2008
Johns Hopkins University
2007
Chulabhorn Research Institute
2007
Stanford University
2003-2005
Lawrence Livermore National Laboratory
2004
The covalent binding of the hepatocarcinogen aflatoxin B1 by rat liver microsomes to calf thymus DNA resulted in a level equal one residue per 60 nucleotides. An derivative-guanine adduct was efficiently liberated from with formic acid. Analytical reversed-phase high-pressure liquid chromatography hydrolysate revealed that approximately 90% carcinogen bound could be accounted for as single component. Preparative used isolate sufficient quantities structural analysis large (340 mg) DNA. A...
The mutagenicity of O6-methylguanine (O6MeGua), a chemical carcinogen-DNA adduct, has been studied in vivo by using single-stranded M13mp8 genome which single O6MeGua residue was positioned the unique recognition site for restriction endonuclease Pst I. Transformation Escherichia coli MM294A cells with this vector gave progeny phage, 0.4% were mutated their I site. In separate experiment, cellular levels O6MeGua-DNA methyltransferase (an O6MeGua-repair protein) depleted treatment...
The human immunodeficiency virus (HIV) replicates its genome and mutates at exceptionally high rates. As a result, the is able to evade immunological chemical antiviral agents. We tested hypothesis that further increase in mutation rate by promutagenic nucleoside analogs would abolish viral replication. evaluated deoxynucleoside for lack of toxicity cells, incorporation HIV reverse transcriptase, resistance repair when incorporated into DNA strand an RNA⋅DNA hybrid, mispairing frequency....
The most common base substitution arising from oxidative damage of DNA is a GC → AT transition. In an effort to determine the oxidized lesion(s) that gives rise this mutation, mutagenicity three cytosines, 5-hydroxycytosine, 5-hydroxyuracil, and uracil glycol, were investigated in Escherichia coli . An M13 viral genome was constructed contain single cytosine at specific site. Replication vivo single-stranded genomes yielded mutation frequencies 0.05%, 83%, 80% for respectively. predominant...
Interstrand DNA cross-link damage is a severe challenge to genomic integrity. Nucleotide excision repair plays some role in the of cross-links caused by psoralens and other agents. However, mammalian cells there evidence that ERCC1-XPF nuclease has specialized additional function during interstrand repair, beyond its nucleotide repair. We placed psoralen monoadduct or duplex, 4–6 bases from junction with unpaired DNA. endonucleolytically cleaved within duplex on either side adduct, strand...
The products of in vivo covalent binding activated aflatoxin B1 (AFB1) to DNA have been investigated rats. principal product formed liver rats treated with AFB1 has identified as 2,3-dihydro-2-(N7-guanyl)-3-hydroxy-aflatoxin B1. This compound was isolated from the dosed (2.0 mg/kg) sufficient quantity for characterization by physicochemical techniques, including field-desorption mass spectrometry. information together results chemical methylation proved that major adduct between and is...
Human cDNA clones encoding a structure-specific recognition protein, SSRP1, that binds specifically to DNA modified with cisplatin have been isolated and characterized. The SSRP1 gene maps human chromosome 11q12. clones, obtained by using partial-length cDNAs described previously, predict an 81-kDa protein containing several highly charged domains stretch of 75 amino acids 47% identical portion the high mobility group (HMG) HMG1. This HMG box most likely constitutes structure element for...
AlkB repairs 1-alkyladenine and 3-methylcytosine lesions in DNA by directly reversing the base damage. Although repair studies with randomly alkylated substrates have been performed, miscoding nature of these related individually bases suppression mutagenesis within cells not yet explored. Here, we address potential 1-methyldeoxyadenosine (m1A), 3-methyldeoxycytidine (m3C), 3-ethyldeoxycytidine (e3C), 1-methyldeoxyguanosine (m1G), 3-methyldeoxythymidine (m3T) synthesizing single-stranded...
<h3>Background and aims:</h3> Hepatocellular carcinoma (HCC) frequently results from synergism between chemical infectious liver carcinogens. Worldwide, the highest incidence of HCC is in regions endemic for foodborne contaminant aflatoxin B1 (AFB1) hepatitis B virus (HBV) infection. Recently, gut microbes have been implicated multisystemic diseases including obesity diabetes. Here, hypothesis that specific intestinal bacteria promote cancer was tested viral transgenic mouse models....
Single-stranded DNA genomes have been constructed that site-specifically contain the 7,8-dihydro-8-oxo-2'-deoxyguanine (8-oxoG) oxidation products guanidinohydantoin (Gh) and two stable stereoisomers of spiroiminodihydantoin (Sp1 Sp2). The circular viral were transfected into wild-type AB1157 Escherichia coli, efficiency lesion bypass by polymerase(s) was assessed. Viral progeny analyzed for mutation frequency type using recently developed restriction endonuclease postlabeling (REAP) assay....
We have determined the x-ray structure of a DNA fragment containing 7,8-dihydro-8-oxoguanine (G(O)). The duplex form d(CCAGOCGCTGG) has been to 1.6-A resolution. results demonstrate that GO forms Watson-Crick base pairs with opposite C and G(O) is in anti conformation. Structural perturbations induced by C.G(O)anti are subtle. allows us identify probable elements which repair protein MutM recognizes its substrates. Hydrogen bond donors/acceptors within major groove most likely element. In...
A G to T mutation has been observed at the third position of codon 249 p53 tumor-suppressor gene in over 50% hepatocellular carcinoma cases associated with high exposure aflatoxin B 1 (AFB ). Hypotheses have put forth that AFB , concert hepatitis virus (HBV), may play a role formation of, and/or selection for, this mutation. The primary DNA adduct is 8,9-dihydro-8-( N 7 -guanyl)-9-hydroxyaflatoxin -N7-Gua), which converted naturally two secondary lesions, an apurinic site and...
Nucleotide excision repair by mammalian enzymes removes DNA damage as part of approximately 30-mer oligonucleotides incising phosphodiester bonds on either side a lesion. We analyzed this dual incision reaction at single 1,3-intrastrand d(GpTpG)-cisplatin cross-link in closed circular duplex substrate. Incisions were formed the with human cell extracts which synthesis was inhibited. The nicks mapped restriction fragment end labeling and primer extension analysis. Principal sites cleavage...
A protein homologous to the Escherichia coli MutY protein, referred as MYH, has been identified in nuclear extracts of calf thymus and human HeLa cells. Western blot (immunoblot) analysis using polyclonal antibodies E. detected a 65 kDa both extracts. Partial purification MYH from cells revealed 65-kDa well functional but apparently degraded form 36 kDa, determined by glycerol gradient centrifugation immunoblotting with anti-MutY antibodies. Calf is DNA glycosylase that specifically removes...