scholarly journals Effect of Chromatin Structure on the Extent and Distribution of DNA Double Strand Breaks Produced by Ionizing Radiation; Comparative Study of hESC and Differentiated Cells Lines

2016 ◽  
Vol 17 (1) ◽  
pp. 58 ◽  
Author(s):  
Priyanka Venkatesh ◽  
Irina Panyutin ◽  
Evgenia Remeeva ◽  
Ronald Neumann ◽  
Igor Panyutin
Keyword(s):  
Ionizing Radiation ◽  
Comparative Study ◽  
Chromatin Structure ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Differentiated Cells

scholarly journals Μελέτη σε επίπεδο ηλεκτρονικής μικροσκοπίας της πρωτεΐνης H2AX που αναγνωρίζει βλάβες του DNA στον ανθρώπινο καρκίνο

2008 ◽  
Author(s):  
Χαρίκλεια Μαρίνου
Keyword(s):  
Dna Repair ◽  
Ionizing Radiation ◽  
Chromatin Structure ◽  
Double Strand Breaks ◽  
Lung Fibroblasts ◽  
Similar Reaction ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Dna Double Helix ◽  
Dna Ends

Eukaryotic DNA is organized into noucleosomes and high order chromatin structure, which plays an important role in the regulation of many nuclear processes including DNA repair. The DNA within our cells is continually being exposed to DNA-damaging agents. These include ultraviolet light, natural and man-made mutagenic chemicals and reactive oxygen species generated by ionizing radiation. Of the various forms of damage that are inflicted by these mutagens, probably the most dangerous is the DNA double strand breaks (DSBs). These are generated when the two complementary strands of the DNA double helix are broken simultaneously at sites that are sufficiently close to one another that base-pairing and chromatin structure are insufficient to keep the two DNA ends juxtaposed. DSBs pose a serious threat to cell viability and genome stability and they are also generated when replication forks encounter blocking lesions. The failure to repair DSBs or misrepair can result in cell death or large-scale chromosome changes including deletions, translocations and chromosome fusions that enhance genome instability and are hallmarks of cancer cells. Cells have evolved groups of proteins that function in signaling networks that sense DSBs, arrest the cell cycle and activate DNA repair pathways. Histone H2AX is a member of the H2A histone family that differs from the other H2A histones by the presence of an evolutionary conserved C-terminal motif. The serine residue in this motif becomes rapidly phosphorylated in cells when DSBs are introduced (γ-H2AX) forming foci. These γ-H2AX foci may play an essential role in the efficient recruitment of proteins involved in the repair of the DNA DSBs. This role may be to mark the site of the damage. It is also possible that the H2AX phosphorylation alters chromatin structure to facilitate repair or to stabilize the break region so that the DNA ends remain in proximity. Given the above, the main purpose of this study was to ultrastructurally localize using immunogold, γ-H2AX foci in human lung fibroblasts irradiated with specific doses of ionizing radiation in order to create DSBs and to examine if a similar reaction takes place in cancer lung cells. The results indicate that when fibroblasts are experimentally exposed to increasing doses of radiation, aggregates of gold particles are observed indicating localization of γ-H2AX foci. In a series of similar experiments using cancer lung tissue, the same pattern of gold particle localization is observed suggesting that in these cells the formation of γ-H2AX foci is triggered. It is the first time ever that γ-H2AX foci formation is ultrastructurally identified with electron microscopy and this is very important since it confirms the existence of foci in chromatin and indicates the sites of DNA double strand breaks.

Effects of melatonin on repair of DNA double strand breaks caused by ionizing radiation in rat peripheral blood

2016 ◽  
Vol 9 (4) ◽  
pp. 821-827 ◽  
Author(s):  
Majid Valizadeh ◽  
Alireza Shirazi ◽  
Pantea Izadi ◽  
Javad Tavakkoli Bazzaz ◽  
Hamed Rezaeejam ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Peripheral Blood ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks

Higher-Order Chromatin Structure-Dependent Repair of DNA Double-Strand Breaks: Factors Affecting Elution of DNA from Nucleoids

1998 ◽  
Vol 149 (6) ◽  
pp. 533 ◽  
Author(s):  
P. J. Johnston ◽  
S. H. MacPhail ◽  
J. P. Banáth ◽  
P. L. Olive ◽  
J. P. Banath
Keyword(s):  
Chromatin Structure ◽  
Higher Order ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Factors Affecting ◽  
Strand Breaks

scholarly journals βarrestin-1 regulates DNA repair by acting as an E3-ubiquitin ligase adaptor for 53BP1

2019 ◽  
Vol 27 (4) ◽  
pp. 1200-1213 ◽  
Author(s):  
Ainhoa Nieto ◽  
Makoto R. Hara ◽  
Victor Quereda ◽  
Wayne Grant ◽  
Vanessa Saunders ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Strand Break ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Molecular Scaffold ◽  
Strand Breaks

Abstract Cellular DNA is constantly under threat from internal and external insults, consequently multiple pathways have evolved to maintain chromosomal fidelity. Our previous studies revealed that chronic stress, mediated by continuous stimulation of the β2-adrenergic-βarrestin-1 signaling axis suppresses activity of the tumor suppressor p53 and impairs genomic integrity. In this pathway, βarrestin-1 (βarr1) acts as a molecular scaffold to promote the binding and degradation of p53 by the E3-ubiquitin ligase, MDM2. We sought to determine whether βarr1 plays additional roles in the repair of DNA damage. Here we demonstrate that in mice βarr1 interacts with p53-binding protein 1 (53BP1) with major consequences for the repair of DNA double-strand breaks. 53BP1 is a principle component of the DNA damage response, and when recruited to the site of double-strand breaks in DNA, 53BP1 plays an important role coordinating repair of these toxic lesions. Here, we report that βarr1 directs 53BP1 degradation by acting as a scaffold for the E3-ubiquitin ligase Rad18. Consequently, knockdown of βarr1 stabilizes 53BP1 augmenting the number of 53BP1 DNA damage repair foci following exposure to ionizing radiation. Accordingly, βarr1 loss leads to a marked increase in irradiation resistance both in cells and in vivo. Thus, βarr1 is an important regulator of double strand break repair, and disruption of the βarr1/53BP1 interaction offers an attractive strategy to protect cells against high levels of exposure to ionizing radiation.

Methylproamine protects against ionizing radiation by preventing DNA double-strand breaks

2010 ◽  
Vol 692 (1-2) ◽  
pp. 49-52 ◽  
Author(s):  
Carl N. Sprung ◽  
Raja S. Vasireddy ◽  
Tom C. Karagiannis ◽  
Shanon J. Loveridge ◽  
Roger F. Martin ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks
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