The spatial organization of non-homologous end joining: From bridging to end joining

Ochi, Takashi; Wu, Qian; Blundell, Tom L.

doi:10.1016/j.dnarep.2014.02.010

Cited by 63 publications

(60 citation statements)

References 167 publications

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“…These results indicate that the delay of DDR in Hela cells was independent of Ku70 function. This phenomena may be due to the intrinsic structure and property of Ku70 which involve the direct binding to DNA [32]; and may not interfere with Cd (Ku70 DNA binding domain may lack a binding site to Cd or Zn) [33]. Overall, our results indicate that Cd did not affect the formation of Ku70 foci, and raise the question whether other NHEJ-related factors may be impaired by Cd, following X-ray-induced DSBs.…”

Section: Discussionmentioning

confidence: 70%

Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA-PKcs phosphorylation and downregulation of XRCC4 and Ligase IV

Zhang

et al. 2015

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Section: Discussionmentioning

confidence: 70%

Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA-PKcs phosphorylation and downregulation of XRCC4 and Ligase IV

Zhang

et al. 2015

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…4). Readers should also refer to detailed reviews about the structural aspects of the interactions of Ligase IV with XRCC4, XLF, and Artemis (113,114). However, we still lack a convincing comprehensive view of how the enzymatic components are positioned at a single DNA end or at a pair of DNA ends.…”

Section: Structural Biology Of Nhejmentioning

confidence: 99%

Nonhomologous DNA end-joining for repair of DNA double-strand breaks

Pannunzio

Watanabe

Lieber

2018

Journal of Biological Chemistry

386

360

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Nonhomologous DNA end joining (NHEJ) is the predominant DSB repair pathway throughout the cell cycle and accounts for nearly all DSB repair outside of the S and G2 phases. NHEJ relies on Ku to thread onto DNA termini and thereby improve the affinity of the NHEJ enzymatic components consisting of polymerases (Pol m and Pol l), a nuclease (the Artemis·DNA-PKcs complex), and a ligase (XLF·XRCC4·Lig4 complex). Each of the enzymatic components is distinctive for its versatility in acting on diverse incompatible DNA end configurations coupled with a flexibility in loading order, resulting in many possible junctional outcomes from one DSB. DNA ends can either be directly ligated or, if the ends are incompatible, processed until a ligatable configuration is achieved that is often stabilized by up to 4 bp of terminal microhomology. Processing of DNA ends results in nucleotide loss or addition, explaining why DSBs repaired by NHEJ are rarely restored to their original DNA sequence. Thus, NHEJ is a single pathway with multiple enzymes at its disposal to repair DSBs, resulting in a diversity of repair outcomes.

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“…Once Cdk2 activity initiates DNA replication, DSBs can trigger entirely different signalling responses as some broken ends are not 'simply' religated by NHEJ (for a review, see Ochi et al, 2014;Deriano and Roth, 2013) but instead are repaired by HR, which involves the extensive 59-39 resection of the broken ends to produce a 39 overhang. The process of DNA end-resection commits repair to HR and is tightly controlled such that HR only takes place when a sister template is available in S-or G2-phase (Ira et al, 2004).…”

Section: S-phasementioning

confidence: 99%

The same, only different – DNA damage checkpoints and their reversal throughout the cell cycle

Shaltiël

Krenning

Bruinsma

et al. 2015

Journal of Cell Science

254

272

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Cell cycle checkpoints activated by DNA double-strand breaks (DSBs) are essential for the maintenance of the genomic integrity of proliferating cells. Following DNA damage, cells must detect the break and either transiently block cell cycle progression, to allow time for repair, or exit the cell cycle. Reversal of a DNA-damageinduced checkpoint not only requires the repair of these lesions, but a cell must also prevent permanent exit from the cell cycle and actively terminate checkpoint signalling to allow cell cycle progression to resume. It is becoming increasingly clear that despite the shared mechanisms of DNA damage detection throughout the cell cycle, the checkpoint and its reversal are precisely tuned to each cell cycle phase. Furthermore, recent findings challenge the dogmatic view that complete repair is a precondition for cell cycle resumption. In this Commentary, we highlight cell-cycle-dependent differences in checkpoint signalling and recovery after a DNA DSB, and summarise the molecular mechanisms that underlie the reversal of DNA damage checkpoints, before discussing when and how cell fate decisions after a DSB are made.

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The spatial organization of non-homologous end joining: From bridging to end joining

Abstract: HighlightsStructural analyses of NHEJ suggest mechanisms of DNA double-strand break repair.Complexes of Artemis with LigIV and DNA-PK define spatiotemporal relationships.Disease-causing mutations in Artemis, LigIV and XLF are explained by 3D structure.

Cited by 63 publications

References 167 publications

Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA-PKcs phosphorylation and downregulation of XRCC4 and Ligase IV

Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA-PKcs phosphorylation and downregulation of XRCC4 and Ligase IV

Nonhomologous DNA end-joining for repair of DNA double-strand breaks

The same, only different – DNA damage checkpoints and their reversal throughout the cell cycle

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