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Friedland, W. ; Jacob, P. ; Kundrát, P.

Stochastic simulation of DNA double-strand break repair by non-homologous end joining based on track structure calculations.

Radiat. Res. 173, 677-688 (2010)
Verlagsversion DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
A Monte Carlo simulation model for DNA repair via the non-homologous end-joining pathway has been developed. Initial DNA damage calculated by the Monte Carlo track structure code PARTRAC provides starting conditions concerning spatial distribution of double-strand breaks (DSBs) and characterization of lesion complexity. DNA termini undergo attachment and dissociation of repair enzymes described in stochastic first-order kinetics as well as step-by-step diffusive motion considering nuclear attachment sites. Pairs of DNA termini with attached DNA-PK enter synapsis under spatial proximity conditions. After synapsis, a single rate-limiting step is assumed for clean DNA ends, and step-by-step removal of nearby base lesions and strand breaks is considered for dirty DNA ends. Four simple model scenarios reflecting different hypotheses on the origin of the slow phase of DSB repair have been set up. Parameters for the presynaptic phase have been derived from experimental data for Ku70/Ku80 and DNA-PK association and dissociation kinetics. Time constants for the post-synaptic phase have been adapted to experimental DSB rejoining kinetics for human fibroblasts after (137)Cs gamma irradiation. In addition to DSB rejoining kinetics, the yields of residual DSBs, incorrectly rejoined DSBs, and chromosomal aberrations have been determined as a function of dose and compared with experimental data. Three of the model scenarios obviously overestimate residual DSBs after long-term repair after low-dose irradiation, whereas misrejoined DSBs and chromosomal aberrations are in surprisingly good agreement with measurements.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Heat-labile sites; Monte-Carlo; Human fibroblasts; Chromosome-Aberrations; Rejoining kinetics; Liquid water; DSB repair; Radiation; Model; Cell
ISSN (print) / ISBN 0033-7587
e-ISSN 1938-5404
Zeitschrift Radiation Research
Quellenangaben Band: 173, Heft: 5, Seiten: 677-688 Artikelnummer: , Supplement: ,
Verlag Radiation Research Society
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Protection (ISS)