A5008751957- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Radiation Therapy and Dosimetry
- Carcinogens and Genotoxicity Assessment
- Cancer-related gene regulation
- Genetics and Neurodevelopmental Disorders
- Biochemical and Molecular Research
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- RNA modifications and cancer
- Effects of Radiation Exposure
- CRISPR and Genetic Engineering
- DNA and Nucleic Acid Chemistry
- DNA and Biological Computing
- Cancer-related Molecular Pathways
- Genomics and Chromatin Dynamics
- Renal and related cancers
- Mitochondrial Function and Pathology
- Molecular Biology Techniques and Applications
- Plant Genetic and Mutation Studies
- Anesthesia and Neurotoxicity Research
- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- Science, Research, and Medicine
- Microtubule and mitosis dynamics
Oregon Health & Science University
2013-2023
Zekai Tahir Burak Kadın Sağlığı Eğitim ve Araştırma Hastanesi
2016
University of Washington
1983-2006
Oregon State University
2005
Laboratory of Molecular Genetics
2003
University of Kentucky
1989-1998
Markey Cancer Center
1989-1997
Swansea University
1987
University of Colorado Health
1985-1987
University of Colorado Denver
1986-1987
Disruption of the BRCA1 tumor suppressor can be caused not only by inherited mutations in familial cancers but also gene silencing sporadic cancers. Hypoxia, a key feature microenvironment, has been shown to downregulate at transcriptional level via repressive E2F4/p130 complexes. Here we showed that hypoxia drives epigenetic modification promoter, with decreased H3K4 methylation as produced lysine-specific histone demethylase LSD1. We observed increased H3K9 coupled acetylation. Similar...
Silencing of MLH1 is frequently seen in sporadic colorectal cancers. We show here that hypoxia causes decreased histone H3 lysine 4 (H3K4) methylation at the promoter via action H3K4 demethylases LSD1 and PLU-1 promotes durable long-term silencing a pathway requires LSD1. Knockdown or its corepressor, CoREST, also prevents resilencing (and associated cytosine DNA methylation) endogenous RKO colon cancer cells following transient reactivation by treatment with methyltransferase inhibitor...
The radiation environment in deep space includes the galactic cosmic with different proportions of all naturally occurring ions from protons to uranium. Most experimental animal studies for assessing biological effects charged particles have involved acute dose delivery single and/or fractionated exposure protocols. Here, we assessed behavioral and cognitive performance female male C57BL/6J x DBA2/J F1 (B6D2F1) mice two months following rapidly delivered, sequential irradiation (1 GeV, 60%),...
Astronauts are exposed to 56Fe ions that may pose a significant health hazard during and following prolonged missions in deep space. We showed previously object recognition requiring the hippocampus, structure critical for cognitive function, is affected 2-month-old mice irradiated with ions. Here we examined 6-month-old ions, biological age more relevant typical ages of astronauts. Moreover, because mechanisms mediating detrimental effects on hippocampal function unclear, changes networks...
A cis-acting methylation center that signals<i>de novo</i> DNA is located upstream of the mouse<i>Aprt</i> gene. In current study, two approaches were taken to determine if tandem B1 repetitive elements found at 3′ end contribute signal. First, bisulfite genomic sequencing demonstrated CpG sites within methylated relative levels 43% in embryonal stem cells deficient for maintenance methyltransferase when compared with wild type cells. Second, ability signal <i>de upon stable transfection...
The promoter region of the mouse adenine phosphoribosyltransferase (aprt) gene contains one nonconsensus Sp1 binding site at its 5′ end followed by three consensus sites. two 3′-most sites are sufficient for maximal expression aprt, suggesting that non-consensus and redundant. However, 3′ not to block epigenetic inactivation, which led hypothesis redundant and/or required inactivation events. To test this hypothesis, constructs were made in mutated alone or tandem, then each construct was...
A 2.1-kilobase pair region located just upstream of the mouse aprt (adenine phosphoribosyltransferase) gene has a methylation pattern that is conserved in tissues and culture cell lines. This includes four HpaII/MspI sites. Two these sites are fully methylated, one partially unmethylated. Transfection experiments have demonstrated can be reproduced embryonal carcinoma stem line via de novo (Turker, M.S., Mummaneni, P., Bishop, P.L. (1991) Somat. Cell Mol. Genet. 17, 151-157). To examine...
Proton irradiation poses a potential hazard to astronauts during and following mission, with post-mitotic cells at most risk because they cannot dilute resultant epigenetic changes via cell division. Persistent that result from environmental exposures include gains or losses of DNA methylation cytosine, which can impact gene expression. In the present study, we compared long-term effects whole body proton in mouse hippocampus left ventricle. We used an unbiased genome-wide involving ChIP-seq...
The radiation environment astronauts are exposed to in deep space includes galactic cosmic (GCR) with different proportions of all naturally occurring ions. To assist NASA assessment risk the brain following exposure a mixture ions broadly representative GCR, we assessed behavioral and cognitive performance female male C57BL/6J x DBA2/J F1 (B6D2F1) mice two months rapidly delivered, sequential 6 beam irradiation protons (1 GeV, LET = 0.24 keV, 50%), 4He (250 MeV/n, 1.6 keV/m, 20%), 16O LET=...
Abstract Seventy‐four sporadic ovarian tumors were studied for loss of heterozygosity (LOH) and microsatellite instability (MI) with 20 polymorphic markers on chromosome 17 at least I marker every other chromosome. Additionally, activation the K‐ras oncogene was examined through mutation analysis codon 12. A majority analyzed low grade and/or mucinous histologic type. negative correlation between LOH K‐ ras observed, former alteration present in high serous endometrioid latter most commonly...
In this report we test the hypothesis that a cis-acting methylation center can induce epigenetic gene inactivation. The element used is an 838-base pair fragment was shown previously to provide de novo signal (Mummaneni, P., Bishop, P. L., and Turker, M. S.(1993) J. Biol. Chem. 268, 552-558). Its normal location approximately 1.3 kilobase pairs upstream of mouse aprt (adenine phosphoribosyltransferase) gene. To determine if could inactivation gene, plasmid construct created in which moved...
Background Aberrant epigenetic silencing plays a major role in cancer formation by inactivating tumor suppressor genes. While the endpoints of aberrant are known, i.e., promoter region DNA methylation and altered histone modifications, triggers not known. We used tet-off system to test hypothesis that transient reduction gene expression will sensitize undergo silencing. Methodology/Principal Findings The tet responsive (PTRE) was drive selectable human HPRT cDNA independent transfectants an...
Abstract The frequencies of 6‐thioguanine‐resistant primary clones from the kidneys and skeletal muscles aging male cohorts two F1 hybrid strains Mus musculus varied 0.59 to 10.96 × 10 −5 did not increase as a function donor age (up 40 months). Resistant were shown be severely deficient in activity hypoxanthine‐guanine phosphoribosyltransferase (EC 2.4.2.8). These deficiencies presumably resulted molecular alterations at this X‐linked locus, including point mutations. No X‐chromosome...
Abstract Background The Fanconi anemia (FA) pathway is a multigene DNA damage response network implicated in the repair of lesions that arise during replication or after exogenous damage. FA displays synthetic lethal relationship with certain genes such as ATM (Ataxia Telangectasia Mutated) are frequently mutated tumors. Thus, inhibition FANCD2 monoubiquitylation (FANCD2-Ub), key step pathway, might target tumor cells defective through interaction. Curcumin was previously identified weak...