2016
DOI: 10.1093/abbs/gmw046
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Abstract: DNA double-strand breaks (DSBs) are the most serious form of DNA damage. In human cells, non-homologous end joining (NHEJ) is the major pathway for the repair of DSBs. Different types of DSBs result in different subsets of NHEJ repair strategies. These variations in NHEJ repair strategies depend on numerous elements, such as the flexible recruitment of NHEJ-related proteins, the complexity of the DSB ends, and the spatial-and temporal-ordered formation of the multiprotein complex. On the one hand, current stud… Show more

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Cited by 40 publications
(35 citation statements)
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“…In this work we use an in silico model to test the compatibility of several experimentally supported mechanisms hypothesised to operate at distinct stages along the pathway. We determine that the mechanisms proposed by Graham et al (Graham et al, 2016), Lee et al (Lee et al, 2015), and Uematsu et al (Uematsu et al, 2007) can be incorporated into a theory of sequential joining of the major canonical NHEJ proteins (Lieber, 2010;Yang et al, 2016;Li et al, 2014) to reproduce experimentally observed fluorescent foci kinetics. However, we highlight specific biological mechanisms which are not clearly defined experimentally.…”
Section: Resultsmentioning
confidence: 99%
“…In this work we use an in silico model to test the compatibility of several experimentally supported mechanisms hypothesised to operate at distinct stages along the pathway. We determine that the mechanisms proposed by Graham et al (Graham et al, 2016), Lee et al (Lee et al, 2015), and Uematsu et al (Uematsu et al, 2007) can be incorporated into a theory of sequential joining of the major canonical NHEJ proteins (Lieber, 2010;Yang et al, 2016;Li et al, 2014) to reproduce experimentally observed fluorescent foci kinetics. However, we highlight specific biological mechanisms which are not clearly defined experimentally.…”
Section: Resultsmentioning
confidence: 99%
“…Damage to DNA integrity is part of normal homeostasis or cellular changes involved in meiosis, cell division or immunoglobulin and T cell receptor recombination (Yang et al 2016). Increased damage may also be inflicted by ionizing radiation or chemical compounds.…”
Section: Discussionmentioning
confidence: 99%
“…A compact collapsed thymic epithelial reticulated network devoid of lymphocytes is shown, and Hassall's corpuscles can be seen in the medulla. a complex of 5 proteins including DNA-PKcs, Ku70, Ku80 as well as XRCC4 and LIG4 (Yang et al 2016). Impairment in any of these proteins results in ablated capacity to carry out V(D)J gene rearrangement that is essential for creation of a full TCR and BCR repertoire (Slatter and Gennery 2010).…”
Section: Discussionmentioning
confidence: 99%
“…The repair pathway that is used is influenced by the nature of the break. Since these repair processes have been reviewed extensively recently [15,16,17], they will simply be summarised here. c-NHEJ is the main repair pathway used for the repair of simple DSBs in G1, since G1 cells have no sister chromatids so that HR is not an option.…”
Section: Repair Of Dsbsmentioning
confidence: 99%