How Broken DNA Finds Its Template for Repair: A Computational Approach

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Version: Author's accepted manuscript
Serval ID
serval:BIB_8A0E7CCF0A14
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
How Broken DNA Finds Its Template for Repair: A Computational Approach
Journal
Progress of Theoretical Physics Supplement
Author(s)
Gehlen Lutz R., Gasser Susan M., Dion Vincent
ISSN
0375-9687
Publication state
Published
Issued date
2011
Volume
191
Pages
20-29
Language
english
Notes
Gehlen01122011
Abstract
Homologous recombination (HR) is the process by which a double-strand break in DNA is repaired using an identical donor template. Despite rapid progress in identifying the functions of the proteins that mediate HR, little is known about how broken DNA finds its homologous template. This process, coined homology search, has been difficult to monitor experimentally. Therefore, we present here a computational approach to model the effect of subnuclear positioning and chromatin dynamics on homology search. We found that, in our model, homology search occurs more efficiently if both the cut site and its template are at the nuclear periphery, whereas restricting the movement of the template or the break alone to the periphery markedly increases the time of the search. Immobilization of either component at any position slows down the search. Based on these results, we propose a new model for homology search, the facilitated random search model, which predicts that the search is random, but that nuclear organization and dynamics strongly influence its speed and efficiency.
Keywords
Physics and Astronomy (miscellaneous)
Open Access
Yes
Create date
01/11/2016 15:44
Last modification date
20/08/2019 15:48
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