Epigenetic Gene Silencing is a Novel Mechanism Involved in Delayed Manifestation of Radiation-Induced Genomic Instability in Mammalian Cells

2011 ◽  
Vol 175 (4) ◽  
pp. 416-423 ◽  
Author(s):  
Keiji Suzuki ◽  
Hiroko Yamaji ◽  
Shinko Kobashigawa ◽  
Rie Kawauchi ◽  
Kazutaka Shima ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Genomic Instability ◽  
Mammalian Cells ◽  
Epigenetic Gene Silencing ◽  
Radiation Induced

scholarly journals From aging to cancer: a DNA methylation journey

2012 ◽  
Vol 3 (1) ◽  
pp. 4
Author(s):  
Natalia Puig ◽  
Ruben Agrelo
Keyword(s):  
Dna Methylation ◽  
Gene Silencing ◽  
Genomic Instability ◽  
Neoplastic Transformation ◽  
Promoter Hypermethylation ◽  
Premature Aging ◽  
Global Dna Methylation ◽  
Major Step ◽  
Normal Tissues ◽  
Epigenetic Gene Silencing

Epigenetic gene silencing through DNA promoter hypermethylation is now recognised<strong> </strong>as a major step in the neoplastic transformation of the cell. The methylation levels of several genes increase with age in normal tissues such as the prostate or colon. Genes like <em>WRN </em>or<em> LMNA </em>that are involved in progeria,a premature aging disease <em>WRN and LMNA, </em>are epigenetically inactivated in cancer. In both aging and cancer, global DNA methylation decreases, potentially accounting for the characteristic genomic instability of these processes. In this review, we will focus on how the accumulation of changes in DNA methylation during aging impact tumourigenesis.

scholarly journals Replication Past the -Radiation-Induced Guanine-Thymine Cross-Link G[8,5-Me]T by Human and Yeast DNA Polymerase

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Paromita Raychaudhury ◽  
Ashis K. Basu
Keyword(s):  
Dna Polymerase ◽  
Mammalian Cells ◽  
Translesion Synthesis ◽  
Kidney Cells ◽  
Equal Frequency ◽  
Cross Link ◽  
Dominant Mutation ◽  
Human Embryonic Kidney Cells ◽  
Radiation Induced

-Radiation-induced intrastrand guanine-thymine cross-link, G[8,5-Me]T, hinders replicationin vitroand is mutagenic in mammalian cells. Herein we reportin vitrotranslesion synthesis of G[8,5-Me]T by human and yeast DNA polymerase (hPol and yPol ). dAMP misincorporation opposite the cross-linked G by yPol was preferred over correct incorporation of dCMP, but further extension was 100-fold less efficient for :A compared to :C. For hPol , both incorporation and extension were more efficient with the correct nucleotides. To evaluate translesion synthesis in the presence of all four dNTPs, we have developed a plasmid-based DNA sequencing assay, which showed that yPol was more error-prone. Mutational frequencies of yPol and hPol were 36% and 14%, respectively. Targeted was the dominant mutation by both DNA polymerases. But yPol induced targeted in 23% frequency relative to 4% by hPol . For yPol , targeted and constituted 83% of the mutations. By contrast, with hPol , semi-targeted mutations (7.2%), that is, mutations at bases near the lesion, occurred at equal frequency as the targeted mutations (6.9%). The kind of mutations detected with hPol showed significant similarities with the mutational spectrum of G[8,5-Me]T in human embryonic kidney cells.

Commentary on radiation-induced bystander effects

2004 ◽  
Vol 23 (2) ◽  
pp. 91-94 ◽  
Author(s):  
Eric G Wright
Keyword(s):  
Free Radical ◽  
Ionizing Radiation ◽  
Genomic Instability ◽  
Inflammatory Responses ◽  
Genetic Alterations ◽  
Bystander Effects ◽  
Intercellular Signalling ◽  
Radiation Induced ◽  
Radical Generation ◽  
In Cells

The paradigm of genetic alterations being restricted to direct DNA damage after exposure to ionizing radiation has been challenged by observations in which effects of ionizing radiation arise in cells that in themselves receive no radiation exposure. These effects are demonstrated in cells that are the descendants of irradiated cells (radiation-induced genomic instability) or in cells that are in contact with irradiated cells or receive certain signals from irradiated cells (radiation-induced bystander effects). Bystander signals may be transmitted either by direct intercellular communication through gap junctions, or by diffusible factors, such as cytokines released from irradiated cells. In both phenomena, the untargeted effects of ionizing radiation appear to be associated with free radical-mediated processes. There is evidence that radiation-induced genomic instability may be a consequence of, and in some cell systems may also produce, bystander interactions involving intercellular signalling, production of cytokines and free radical generation. These processes are also features of inflammatory responses that are known to have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. Thus, radiation-induced genomic instability and untargeted bystander effects may reflect interrelated aspects of inflammatory type responses to radiation-induced stress and injury and contribute to the variety of the pathological consequences of radiation exposures.

Sign in / Sign up

Export Citation Format

Share Document