title: Modeling non-homologous end joining.
abstract: Non-homologous end joining (NHEJ) is an important DNA repair pathway for DNA double-strand breaks. Several proteins, including Ku, DNA-PKcs, Artemis, XRCC4/Ligase IV and XLF, are involved in the NHEJ for the DNA damage detection, DNA free end processing and ligation. The classical model of NHEJ is a sequential model in which DNA-PKcs is first recruited by the Ku bound DNA prior to any other repair proteins. Recent experimental study (McElhinny et al., 2000; Costantini et al., 2007; Mari et al., 2006; Yano and Chen, 2008) suggested that the recruitment ordering is not crucial. In this work, by proposing a mathematical model in terms of biochemical reaction network and performing stability and related analysis, we demonstrate theoretically that if DSB repair pathway independent of DNA-PKcs exists, then the classical sequential model and new two-phase model are essentially indistinguishable in the sense that DSB can be repaired thoroughly in both models when the repair proteins are sufficient.
authors.affiliation: USRA, Division of Space Life Sciences, Houston, TX 77058, United States. li@dsls.usra.edu
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Li
authors.forename: Francis A
authors.initials: FA
authors.lastname: Cucinotta
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000072200:Ku Autoantigen; D008957:Models, Genetic; D015398:Signal Transduction / Q000502:physiology
chemical_list: D034961:Antigens, Nuclear; C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D045643:DNA Repair Enzymes