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A comparison of DNA damage probes in two HMEC lines with X-irradiation

Description: In this study, we investigated {gamma}H2AX{sup ser139} and 53BP1{sup ser25}, DNA damage pathway markers, to observe responses to radiation insult. Two Human Mammary Epithelial Cell (HMEC) lines were utilized to research the role of immortalization in DNA damage marker expression, HMEC HMT-3522 (S1) with an infinite lifespan, and a subtype of HMEC 184 (184V) with a finite lifespan. Cells were irradiated with 50 cGy X-rays, fixed with 4% paraformaldehyde after 1 hour repair at 37 C, and processed… more
Date: January 19, 2007
Creator: Wisnewski, Christy L.; Bjornstad, Kathleen A.; Rosen, ChristoperJ.; Chang, Polly Y. & Blakely, Eleanor A.
Partner: UNT Libraries Government Documents Department
open access

Nonhomologous Mechanisms of Repair of Chromosomal Breaks

Description: Discovered three new proteins involved in DNA damage assessment. Interestingly they are all proteins involved in recombination, but they have very different roles in that process and other proteins that might be expected to be equivalently involved are not. This is developing into a very significant area of research.
Date: December 19, 2001
Creator: Haber, J. E.
Partner: UNT Libraries Government Documents Department
open access

Use of Computational Modeling to Evaluate Hypotheses About the Molecular and Cellular Mechanisms of Bystander Effects

Description: This report describes the development of a computational systems biology approach to evaluate the hypotheses of molecular and cellular mechanisms of adaptive response to low dose ionizing radiation. Our concept is that computational models of signaling pathways can be developed and linked to biologically based dose response models to evaluate the underlying molecular mechanisms which lead to adaptive response. For development of quantitatively accurate, predictive models, it will be necessary t… more
Date: November 21, 2006
Creator: Zhao, Yuchao; Conolly, Rory B & Andersen, Melvin E.
Partner: UNT Libraries Government Documents Department
open access

A prospective study of XRCC1 haplotypes and their interaction with plasma carotenoids on breast cancer risk

Description: The XRCC1 protein is involved in the base excision repair pathway through interactions with other proteins. Polymorphisms in the XRCC1 gene may lead to variation in repair proficiency and confer inherited predisposition to cancer. We prospectively assessed the associations between polymorphisms and haplotypes in XRCC1 and breast cancer risk in a nested case-control study within the Nurses' Health Study (incident cases, n 1004; controls, n 1385). We further investigated gene-environment interact… more
Date: January 15, 2004
Creator: Mohrenweiser, H W; Han, J; Hankinson, S E; De Vivo, I; Spiegelman, D; Tamimi, R M et al.
Partner: UNT Libraries Government Documents Department
open access

The Life-cycle of Operons

Description: Operons are a major feature of all prokaryotic genomes, buthow and why operon structures vary is not well understood. To elucidatethe life-cycle of operons, we compared gene order between Escherichiacoli K12 and its relatives and identified the recently formed anddestroyed operons in E. coli. This allowed us to determine how operonsform, how they become closely spaced, and how they die. Our findingssuggest that operon evolution may be driven by selection on geneexpression patterns. First, both … more
Date: March 15, 2007
Creator: Price, Morgan N.; Arkin, Adam P. & Alm, Eric J.
Partner: UNT Libraries Government Documents Department
open access

Repair of radiation-induced heat-labile sites is independent of DNA-PKcs, XRCC1 or PARP

Description: Ionizing radiation induces a variety of different DNA lesions: in addition to the most critical DNA damage, the DSB, numerous base alterations, SSBs and other modifications of the DNA double-helix are formed. When several non-DSB lesions are clustered within a short distance along DNA, or close to a DSB, they may interfere with the repair of DSBs and affect the measurement of DSB induction and repair. We have previously shown that a substantial fraction of DSBs measured by pulsed-field gel elec… more
Date: April 29, 2008
Creator: Stenerlöw, Bo; Karlsson, Karin H.; Radulescu, Irina; Rydberg, Bjorn & Stenerlow, Bo
Partner: UNT Libraries Government Documents Department
open access

DNA Damage Quantitation by Alkaline Gel Electrophoresis.

Description: Physical and chemical agents in the environment, those used in clinical applications, or encountered during recreational exposures to sunlight, induce damages in DNA. Understanding the biological impact of these agents requires quantitation of the levels of such damages in laboratory test systems as well as in field or clinical samples. Alkaline gel electrophoresis provides a sensitive (down to {approx} a few lesions/5Mb), rapid method of direct quantitation of a wide variety of DNA damages in … more
Date: March 24, 2004
Creator: Sutherland, B. M.; Bennett, P. V. & Sutherland, J. C.
Partner: UNT Libraries Government Documents Department
open access

Inhibition of TGFbeta1 Signaling Attenutates ATM Activity inResponse to Genotoxic Stress

Description: Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). Transforming growth factor {beta}1 (TGF{beta}), which is activated by radiation, is a potent and pleiotropic mediator of physiological and pathological processes. Here we show that TGF{beta} inhibition impedes the canonical cellular DNA damage stress response. Irradiated Tgf{beta}1 null murine epithelial cells or human epitheli… more
Date: September 15, 2006
Creator: Kirshner, Julia; Jobling, Michael F.; Pajares, Maria Jose; Ravani, Shraddha A.; Glick, Adam B.; Lavin, Martin J. et al.
Partner: UNT Libraries Government Documents Department
open access

Analysis of Gene Targeting & Nonhomologous End-joining. Final Report

Description: Overall, we identified a number of new proteins that participate in nonhomologous end-joining and also in telomere addition to the ends of broken chromosomes. We showed that NHEJ is severely reduced in cells expressing both yeast mating-type genes and then went on to identify the NEJ1 gene that was under this control. We showed the epistasis relations among a set of mutations that impair telomere addition and we showed that there are in fact two pathways to repair broken chromosomes in the abse… more
Date: November 30, 2002
Creator: Haber, J. E.
Partner: UNT Libraries Government Documents Department
open access

The Sorcerer II Global Ocean Sampling Expedition: Expanding the Universe of Protein Families

Description: Metagenomics projects based on shotgun sequencing of populations of micro-organisms yield insight into protein families. We used sequence similarity clustering to explore proteins with a comprehensive dataset consisting of sequences from available databases together with 6.12 million proteins predicted from an assembly of 7.7 million Global Ocean Sampling (GOS) sequences. The GOS dataset covers nearly all known prokaryotic protein families. A total of 3,995 medium- and large-sized clusters cons… more
Date: March 23, 2006
Creator: Yooseph, Shibu; Sutton, Granger; Rusch, Douglas B.; Halpern, Aaron L.; Williamson, Shannon J.; Remington, Karin et al.
Partner: UNT Libraries Government Documents Department
open access

Molecular Recognition of DNA Damage Sites by Apurinic/Apyrimidinic Endonucleases

Description: The DNA repair/redox factor AP endonuclease 1 (APE1) is a multifunctional protein which is known to to be essential for DNA repair activity in human cells. Structural/functional analyses of the APE activity is thus been an important research field to assess cellular defense mechanisms against ionizing radiation.
Date: July 28, 2005
Creator: Braun, W. A.
Partner: UNT Libraries Government Documents Department
open access

GENETIC AND MOLECULAR ANALYSIS OF DNA DAMAGE REPAIR AND TOLERANCE PATHWAYS.

Description: Radiation can damage cellular components, including DNA. Organisms have developed a panoply of means of dealing with DNA damage. Some repair paths have rather narrow substrate specificity (e.g. photolyases), which act on specific pyrimidine photoproducts in a specific type (e.g., DNA) and conformation (double-stranded B conformation) of nucleic acid. Others, for example, nucleotide excision repair, deal with larger classes of damages, in this case bulky adducts in DNA. A detailed discussion of … more
Date: July 26, 2001
Creator: Sutherland, B. M.
Partner: UNT Libraries Government Documents Department
open access

Functional characterization of dna repair proteins

Description: Genetic material (DNA) is susceptible to spontaneous decomposition, to attack by reactive chemicals produced naturally in cells, and to assault by environmental and food mutagens. DNA modifications can lead to permanent genetic changes that promote human disease. To combat the deleterious effects of DNA damage, organisms are equipped with DNA repair systems. The focus of our investigations has been to elucidate the details of mammalian DNA repair. These studies have provided important insights … more
Date: February 16, 2000
Creator: Wilson, D. M., III
Partner: UNT Libraries Government Documents Department
open access

Lack of Bystander Effects From High LET Radiation For Early Cytogenetic Endpoints.

Description: The aim of this work was to study radiation-induced bystander effects for early cytogenetic end points in various cell lines using the medium transfer technique after exposure to high- and low-LET radiation. Cells were exposed to 20 MeV/ nucleon nitrogen ions, 968 MeV/nucleon iron ions, or 575 MeV/nucleon iron ions followed by transfer of the conditioned medium from the irradiated cells to unirradiated test cells. The effects studied included DNA double-strand break induction, {gamma}-H2AX focu… more
Date: May 7, 2008
Creator: Groesser, Torsten; Cooper, Brian & Rydberg, Bjorn
Partner: UNT Libraries Government Documents Department
open access

Gordon Research Conference on Genetic Toxicology

Description: Genetic toxicology represents a study of the genetic damage that a cell can incur, the agents that induce such damage, the damage response mechanisms available to cells and organisms, and the potential consequences of such damage. Genotoxic agents are abundant in the environment and are also induced endogenously. The consequences of such damage can include carcinogenesis and teratogenesis. An understanding of genetic toxicology is essential to carry out risk evaluations of the impact of genotox… more
Date: February 15, 2003
Creator: Jeggo, Project Director Penelope
Partner: UNT Libraries Government Documents Department
open access

Molecular Basis for Enhancement of the Meiotic DMCI Recombinase by RAD51AP1

Description: Homologous recombination is needed for meiotic chromosome segregation, genome maintenance, and tumor suppression. RAD51AP1 (RAD51 Associated Protein 1) has been shown to interact with and enhance the recombinase activity of RAD51. Accordingly, genetic ablation of RAD51AP1 leads to enhanced sensitivity to and also chromosome aberrations upon DNA damage, demonstrating a role for RAD51AP1 in mitotic homologous recombination. Here we show physical association of RAD51AP1 with the meiosis-specific r… more
Date: November 5, 2010
Creator: Dray, Eloise; Dunlop, Myun Hwa; Kauppi, Liisa; San Filippo, Joseph; Wiese, Claudia; Tsai, Miaw-Sheue et al.
Partner: UNT Libraries Government Documents Department
open access

FY05 LDRD Fianl Report Investigation of AAA+ protein machines that participate in DNA replication, recombination, and in response to DNA damage LDRD Project Tracking Code: 04-LW-049

Description: The AAA+ proteins are remarkable macromolecules that are able to self-assemble into nanoscale machines. These protein machines play critical roles in many cellular processes, including the processes that manage a cell's genetic material, but the mechanism at the molecular level has remained elusive. We applied computational molecular modeling, combined with advanced sequence analysis and available biochemical and genetic data, to structurally characterize eukaryotic AAA+ proteins and the protei… more
Date: December 4, 2006
Creator: Sawicka, D; de Carvalho-Kavanagh, M S; Barsky, D & Venclovas, C
Partner: UNT Libraries Government Documents Department
open access

XRCC3 ATPase activity is required for normal XRCC3-Rad51C complex dynamics and homologous recombination

Description: Homologous recombinational repair is a major DNA repair pathway that preserves chromosomal integrity by removing double-strand breaks, crosslinks, and other DNA damage. In eukaryotic cells, the Rad51 paralogs (XRCC2, XRCC3, Rad51B, Rad51C, and Rad51D) are involved in this process, although their exact functions are largely undetermined. All five paralogs contain ATPase motifs, and XRCC3 appears to exist in a single complex with Rad51C. To begin to examine the function of this Rad51C-XRCC3 compl… more
Date: February 25, 2004
Creator: Yamada, N; Hinz, J; Kopf, V L; Segalle, K & Thompson, L
Partner: UNT Libraries Government Documents Department
open access

Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

Description: Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP) developed slowly over several days and … more
Date: October 24, 2008
Creator: Coppé, Jean-Philippe; Patil, Christopher; Rodier, Francis; Sun, Yu; Munoz, Denise; Goldstein, Joshua et al.
Partner: UNT Libraries Government Documents Department
open access

7th International Workshop on Microbeam Probes of Cellular Radiation Response

Description: The extended abstracts that follow present a summary of the Proceedings of the 7th International Workshop: Microbeam Probes of Cellular Radiation Response, held at Columbia University’s Kellogg Center in New York City on March 15–17, 2006. These International Workshops on Microbeam Probes of Cellular Radiation Response have been held regularly since 1993 (1–5). Since the first workshop, there has been a rapid growth (see Fig. 1) in the number of centers developing microbeams for radiobiological… more
Date: July 21, 2009
Creator: Brenner, David J.
Partner: UNT Libraries Government Documents Department
open access

MEDICAL AND ENVIRONMENTAL EFFECTS OF UV RADIATION.

Description: Organisms living on the earth are exposed to solar radiation, including its ultraviolet (UV) components (for general reviews, the reader is referred to Smith [1] and Young et al. [2]). UV wavelength regions present in sunlight are frequently designated as UVB (290-320 nm) and UVA (320-400 nm). In today's solar spectrum, UVA is the principal UV component, with UVB present at much lower levels. Ozone depletion will increase the levels of UVB reaching the biosphere, but the levels of UVA will not … more
Date: July 26, 2001
Creator: Sutherland, B. M.
Partner: UNT Libraries Government Documents Department
open access

2010 MICROBIAL STRESS RESPONSE GORDON RESEARCH CONFERENCE, JULY 18-23, 2010

Description: The 2010 Gordon Research Conference on Microbial Stress Responses provides an open and exciting forum for the exchange of scientific discoveries on the remarkable mechanisms used by microbes to survive in nearly every niche on the planet. Understanding these stress responses is critical for our ability to control microbial survival, whether in the context of biotechnology, ecology, or pathogenesis. From its inception in 1994, this conference has traditionally employed a very broad definition of… more
Date: July 23, 2011
Creator: Ades, Sarah
Partner: UNT Libraries Government Documents Department
open access

Analysis of Flow Cytometry DNA Damage Response Protein Activation Kinetics Following X-rays and High Energy Iron Nuclei Exposure

Description: We developed a mathematical method to analyze flow cytometry data to describe the kinetics of {gamma}H2AX and pATF2 phosphorylations ensuing various qualities of low dose radiation in normal human fibroblast cells. Previously reported flow cytometry kinetic results for these DSB repair phospho-proteins revealed that distributions of intensity were highly skewed, severely limiting the detection of differences in the very low dose range. Distributional analysis reveals significant differences bet… more
Date: December 15, 2010
Creator: Association, Universities Space Research; Chappell, Lori J.; Whalen, Mary K.; Gurai, Sheena; Ponomarev, Artem; Cucinotta, Francis A. et al.
Partner: UNT Libraries Government Documents Department
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