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High-LET Patterns of DSBs in DNA Loops, the HPRT Gene and Phosphorylation FociWe present new results obtained with our model based on the track structure and chromatin geometry that predicts the DSB spatial and genomic distributions in a cell nucleus with the full genome represented. The model generates stochastic patterns of DSBs in the physical space of the nucleus filled with the realistic configuration of human chromosomes. The model was re-used to find the distribution of DSBs in a physical volume corresponding to a visible phosphorylation focus believed to be associated with a DSB. The data shows whether there must more than one DSB per foci due to finite size of the visible focus, even if a single DSB is radiochemically responsible for the phosphorylation of DNA in its vicinity. The same model can predict patterns of closely located DSBs in a given gene, or in a DNA loop, one of the large-scale chromatin structures. We demonstrated for the example of the HPRT gene, how different sorts of radiation lead to proximity effect in DSB locations, which is important for modeling gene deletions. The spectrum of intron deletions and total gene deletions was simulated for the HPRT gene. The same proximity effect of DSBs in a loop can hinder DSB restitutions, as parts of the loop between DSBs is deleted with a higher likelihood. The distributions of DSBs and deletions of DNA in a loop are presented.
Document ID
20070021787
Acquisition Source
Johnson Space Center
Document Type
Conference Paper
Authors
Ponomarev, Artem L.
(NASA Johnson Space Center Houston, TX, United States)
Huff, Janice L.
(NASA Johnson Space Center Houston, TX, United States)
Cucinotta, Francis A.
(NASA Johnson Space Center Houston, TX, United States)
Date Acquired
August 23, 2013
Publication Date
July 13, 2007
Subject Category
Life Sciences (General)
Meeting Information
Meeting: 18th Annual NASA Space Radiation Investigators'' Workshop
Location: Rohnert Park, CA
Country: United States
Start Date: July 13, 2007
End Date: July 15, 2007
Sponsors: Universities Space Research Association
Distribution Limits
Public
Copyright
Other

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