A5087128310- DNA Repair Mechanisms
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Genetic factors in colorectal cancer
- DNA and Nucleic Acid Chemistry
- Genetics and Neurodevelopmental Disorders
- RNA and protein synthesis mechanisms
- Genomics and Rare Diseases
- Botanical Research and Chemistry
- Bacteriophages and microbial interactions
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Fungal and yeast genetics research
- Genomics, phytochemicals, and oxidative stress
- Plant Genetic and Mutation Studies
- RNA Research and Splicing
- Neurofibromatosis and Schwannoma Cases
- RNA Interference and Gene Delivery
- Chromosomal and Genetic Variations
- Cardiomyopathy and Myosin Studies
- Advanced biosensing and bioanalysis techniques
- Transgenic Plants and Applications
- Oral Health Pathology and Treatment
- Cancer therapeutics and mechanisms
- Carcinogens and Genotoxicity Assessment
Hospital for Sick Children
2012-2023
SickKids Foundation
2002-2022
University of Toronto
1992-2014
University College London
2011
Great Ormond Street Hospital
2011
Western University
1986-1991
Indiana University School of Medicine
1991
Jawaharlal Nehru University
1982-1986
The Huntington's disease gene (HTT) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of may therefore provide routes for therapies targeting the underlying mutation, an approach is likely applicable to other trinucleotide diseases. HdhQ111 mice exhibit higher levels HTT on a C57BL/6 genetic background (B6.HdhQ111) than 129 (129.HdhQ111). Linkage mapping in (B6x129).HdhQ111 F2 intercross animals identified single quantitative trait locus...
R-loops, transcriptionally-induced RNA:DNA hybrids, occurring at repeat tracts (CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n, are associated with diseases including myotonic dystrophy, Huntington's disease, fragile X Friedreich's ataxia. Many of these repeats bidirectionally transcribed, allowing for single- double-R-loop configurations, where either or both DNA strands may be RNA-bound. R-loops can trigger instability (CTG)·(CAG) repeats, but the mechanism this is unclear. We demonstrate...
Expansions of CTG/CAG trinucleotide repeats, thought to involve slipped DNAs at the cause numerous diseases including myotonic dystrophy and Huntington's disease. By unknown mechanisms, further repeat expansions in transgenic mice carrying expanded tracts require mismatch repair (MMR) proteins MSH2 MSH3, forming MutSβ complex. Using an vitro assay, we investigated effect slip-out size, with lengths 1, 3, or 20 excess CTG as well number slip-outs per molecule, on requirement for human MMR....
Frequencies of sister-chromatid exchanges (SCEs) were measured to study the genotoxicity total aqueous extract betal nut and its tannin on mouse bone-marrow cells in vivo. Betal injected i.p. into mice at doses 12.5, 25 or 50 micrograms/g body weight 50, 100 200 respectively for 5, 10 15 days. induced a dose-related increase frequency SCEs after five daily micrograms. Significant increases also observed animals dosed days with extract. After betel there was no significant induction SCE. Mice...
Ongoing inchworm-like CAG and CGG repeat expansions in brains, arising by aberrant processing of slipped DNAs, may drive Huntington's disease, fragile X syndrome, autism. FAN1 nuclease modifies hyper-expansion rates unknown means. We show that FAN1, through iterative cycles, binds, dimerizes, cleaves yielding striking exo-nuclease pauses along slip-outs: 5′-C↓A↓GC↓A↓G-3′ 5′-C↓T↓G↓C↓T↓G-3′. excision is slower than CTG requires intra-strand A·A T·T mismatches. Fully paired hairpins arrested...
The mechanism of disease-associated (CTG)·(CAG) expansion may involve DNA replication slippage, direction, Okazaki fragment processing, recombination, or repair. A length-dependent bias for expansions is observed in humans affected by a trinucleotide repeat-associated disease. We developed an assay to test the effect direction on instabilities incurred during <i>in vitro</i> (SV40) mediated human cell extracts. This system recapitulates humans. Replication HeLa extracts generated and...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe N2-guanine adduct but not the C8-guanine of N6-adenine adducts formed by 4-nitroquinoline 1-oxide blocks 3'-5' exonuclease action T4 DNA polymeraseG. B. Panigrahi and Ian G. WalkerCite this: Biochemistry 1990, 29, 8, 2122–2126Publication Date (Print):February 27, 1990Publication History Published online1 May 2002Published inissue 27 February 1990https://pubs.acs.org/doi/10.1021/bi00460a023https://doi.org/10.1021/bi00460a023research-articleACS...
The instability of (CTG)•(CAG) repeats can cause >15 diseases including myotonic dystrophy, DM1. Instability arise during DNA replication, repair or recombination, where sealing nicks by ligase I (LIGI) is a final step. role LIGI in CTG/CAG was determined using vitro and vivo approaches. Cell extracts from human (46BR) harbouring deficient (∼3% normal activity) were used to replicate repeats; DM1 mice with >300 CTG crossed the 46BR LigI. In mice, defective LigI reduced frequency expansions...
Constitutional mismatch repair deficiency (CMMRD) is a highly penetrant cancer predisposition syndrome caused by biallelic mutations in (MMR) genes. As several syndromes are clinically similar, accurate diagnosis critical to screening and treatment. genetic confounded 15 or more pseudogenes variants of uncertain significance, robust diagnostic assay urgently needed. We sought determine whether an that directly measures MMR activity could accurately diagnose CMMRD.In vitro was quantified...
Journal Article Sequence effect on incision by (A)BC excinuclease of 4NQO adducts and UV photoproducts Get access David C. Thomas, Thomas * + Present addresses: Laboratory Molecular Genetics, National Institute Environmental Health Sciences, Research Triangle Park, NC 2T7O9 To whom correspondence should be addressed Search for other works this author on: Oxford Academic PubMed Google Scholar Intisar Husain, Husain Stephen G. Chaney, Chaney Gagan B. Panigrahi, Panigrahi 1Department...
The FLP protein that is encoded by the 2-pm plasmid of yeast Saccharomyces cerevisicre a 45-kDa site-specific recombinase belongs to Int family recombination proteins.FLP catalyzes event within binding specifically each three 13-base pair (bp) symmetry elements recognition target (FRT).We have shown previously partial proteolysis proteinase K resulted in COOH-terminal fragment size 32 kDa (P32) and an NH2-terminal 13 (P13).In this study we used footprinting with dimethyl sulfate show P32...
The FLP protein of the 2µm plasmid Saccharomyces cerevisiae promotes conservative site-specific recombination between DNA sequences that contain recognition target (FRT). binds to each three 13 base pair symmetry elements in FRT site a manner. We have probed both major and minor groove contacts using dimethyl sulphate, monoacetyl-4-hydroxyaminoquinoline 1-oxide potassium permanganate find displays extensive interactions with residues grooves 10 pairs element. no evidence assumes...