Double-strand DNA breaks articles within Nature

Featured

  • Article |

    A tandem BRCT-domain-associated ubiquitin-dependent recruitment motif in BARD1 recruits BRCA1 to DNA double-strand breaks (DSBs) to promote homologous recombination and antagonize the 53BP1 DSB repair pathway that mediates non-homologous end joining.

    • Jordan R. Becker
    • , Gillian Clifford
    •  & J. Ross Chapman

  • Article |

    A small proportion of Spo11-dependent DNA double-strand breaks are ‘double cuts’—adjacent breaks that occur in concert—revealing that gap repair during meiosis includes that of DNA gaps generated by Spo11 itself.

    • Dominic Johnson
    • , Margaret Crawford
    •  & Matthew J. Neale

  • Article |

    Double-strand DNA break repair by the non-homologous end joining pathway involves the transition from a complex that bridges the DNA ends to a complex that aligns the DNA for ligation through the dissociation of the kinase subunits of the DNA-PK complexes.

    • Siyu Chen
    • , Linda Lee
    •  & Yuan He

  • Article |

    The PARP2–HPF1 histone-modifying complex bridges two nucleosomes to align broken DNA ends for ligation, initiating conformational changes that activate PARP2 and enable DNA damage repair.

    • Silvija Bilokapic
    • , Marcin J. Suskiewicz
    •  & Mario Halic

  • Letter |

    The specificity of 53BP1 and its co-factors for particular DNA substrates during non-homologous end joining (NHEJ) derives from REV7–shieldin, a four-subunit DNA-binding complex that is required for REV7-dependent NHEJ but not for REV7-dependent DNA interstrand cross-link repair.

    • Hind Ghezraoui
    • , Catarina Oliveira
    •  & J. Ross Chapman

  • Letter |

    The 53BP1 effector complex shieldin is involved in non-homologous end-joining and immunoglobulin class switching, and acts to protect DNA ends to facilitate the repair of DNA by 53BP1.

    • Sylvie M. Noordermeer
    • , Salomé Adam
    •  & Daniel Durocher

  • Letter |

    A cryo-electron microscopy structure of the DNA damage repair protein 53BP1 bound to a nucleosome illuminates the way 53BP1 recognizes two types of histone modifications (a methyl group and a ubiquitin moiety), and provides insight into the highly specified recognition and recruitment of 53BP1 to modified chromatin.

    • Marcus D. Wilson
    • , Samir Benlekbir
    •  & Daniel Durocher

  • Letter |

    Loss of REV7 is shown to regulate end resection of double-stranded DNA breaks in BRCA1-deficient cells, leading to PARP inhibitor resistance and restoration of homologous recombination; REV7 dictates pathway choice in BRCA1-deficient cells and during immunoglobulin class switching.

    • Guotai Xu
    • , J. Ross Chapman
    •  & Sven Rottenberg

  • Letter |

    Next-generation sequencing technology is used to show that the error-prone polymerase θ (Polθ) is needed to promote alternative non-homologous end joining at telomeres, and during chromosomal translocations, while counteracting homologous recombination; inhibition of Polθ represents a potential therapeutic strategy for tumours that have mutations in homology-directed repair genes.

    • Pedro A. Mateos-Gomez
    • , Fade Gong
    •  & Agnel Sfeir

  • Letter |

    Meiotic recombination is initiated by a fairly uniform distribution of hundreds of DNA double-strand breaks catalysed by the Spo11 protein; here, Tel1 (orthologue of human ATM) is shown to be required for the localized inhibition that prevents double-strand breaks from forming close to one another.

    • Valerie Garcia
    • , Stephen Gray
    •  & Matthew J. Neale

  • Letter |

    Endogenous RNA transcripts are shown to mediate recombination with yeast chromosomal DNA; as the level of RNAs in the nucleus is quite high, these results may open up new understanding of the plasticity of repair and genome instability mechanisms.

    • Havva Keskin
    • , Ying Shen
    •  & Francesca Storici

  • Letter |

    BRCA2, the breast cancer susceptibility gene factor, interacts with TREX-2, a protein complex involved in the biogenesis and export of messenger ribonucleoprotein, to process DNA–RNA hybrid structures called R-loops that can trigger genome instability; these may be a central cause of the stress occurring in early cancer cells that drives oncogenesis.

    • Vaibhav Bhatia
    • , Sonia I. Barroso
    •  & Andrés Aguilera

  • Letter |

    The bacterial RecBCD helicase/nuclease shows broad, and apparently static, heterogeneity in the unwinding rate manifest by individual molecules: here it is shown that transiently halting an enzyme during processive translocation allows for a change, most likely conformational, such that the velocity of the molecule after pausing can fall anywhere within the spectrum of rates seen for a population.

    • Bian Liu
    • , Ronald J. Baskin
    •  & Stephen C. Kowalczykowski

  • Article |

    This study shows that 53BP1 recruitment to sites of DNA damage involves dual recognition of H4K20me2 and H2AK15 histone ubiquitination; the ubiquitin mark and the surrounding epitope on H2A are read by a region of 53BP1 designated the ubiquitination-dependent recruitment motif.

    • Amélie Fradet-Turcotte
    • , Marella D. Canny
    •  & Daniel Durocher

  • News & Views |

    The protein Sae2 mediates the repair of double-strand breaks in DNA. It emerges that Sae2 activity is controlled by both its modification with acetyl groups and its degradation by the process of autophagy. See Article p.74

    • Catherine J. Potenski
    •  & Hannah L. Klein

  • Letter |

    Recruitment of 53BP1 to double-strand DNA breaks is an important step in the cellular response to DNA damage. Here, the histone methyltransferase MMSET is shown to be responsible for localized increases in a histone modification that is involved in recruiting 53BP1. The mechanism of MMSET recruitment to DNA damage sites is also investigated.

    • Huadong Pei
    • , Lindsey Zhang
    •  & Zhenkun Lou

  • Letter |

    Although loss of XLF, a classical non-homologous DNA end-joining (NHEJ) repair factor, shows strong effects in non-lymphoid cells, in lymphoid cells its absence has only modest effects on V(D)J recombination. This study now shows that in lymphoid cells, two other repair factors — ATM kinase and histone protein H2AX — have functional redundancy with XLF. Thus, mice deficient in both ATM and XLF have compromised conventional NHEJ, although alternative end-joining is retained. The results hint that the redundant function in end-joining that XLF has with both ATM and H2AX may have to do with an ATM role in chromatin accessibility.

    • Shan Zha
    • , Chunguang Guo
    •  & Frederick W. Alt

  • News & Views |

    Purification of the human tumour-suppressor protein BRCA2, which is crucial for DNA repair, has been a formidable challenge owing to its large size. That mission is now accomplished, providing biochemical insight. See Article p.678

    • Lee Zou

  • Article |

    When double-strand breaks occur in eukaryotic DNA, the chromatin that protects and organizes the genome must be removed from the vicinity of the break to allow repair factors to bind. Such chromatin displacement involves the addition of ubiquitin groups to histone proteins near the break by the ubiquitin ligases RNF8 and RNF168. Here it is shown that the enzyme OTUB1 prevents RNF168-dependent poly-ubiquitination. Pharmacological targeting of this process might enhance the DNA damage response.

    • Shinichiro Nakada
    • , Ikue Tai
    •  & Daniel Durocher

  • Letter |

    Most agents that generate breaks in DNA leave 'dirty ends' that cannot be joined immediately; instead, intervening steps are required to restore the integrity of nucleotides at the break. Here it is shown that the non-homologous end joining pathway requires a 5′-dRP/AP lyase activity to remove abasic sites at double-strand breaks. Surprisingly, this activity is catalysed by the Ku70 protein, which, together with its partner Ku86, had been thought only to recognize broken DNA ends and to recruit other factors that process ends.

    • Steven A. Roberts
    • , Natasha Strande
    •  & Dale A. Ramsden

  • Letter |

    In meiotic cells paired homologues are joined by a set of crossovers known as a double Holliday junction (DHJ). Whether DHJs form during mitotic recombination has been unclear, as mitotic cells possess alternative repair pathways that would not require DHJ formation. Here it is demonstrated that mitotic and meiotic cells form similar DHJs, but that the levels in mitotic cells are approximately 10–fold lower, and show a preference for joints between sister chromatids rather than homologues. Consequently, in mitotic cells non–crossover outcomes are favoured.

    • Malgorzata Bzymek
    • , Nathaniel H. Thayer
    •  & Neil Hunter

Browse broader subjects

Browse Double-strand DNA breaks across other nature.com journals