DNA damage response articles within Nature

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  • Article
    | Open Access

    Learning results in persistent double-stranded DNA breaks, nuclear rupture and release of DNA fragments and histones within hippocampal CA1 neurons that, following TLR9-mediated DNA damage repair, results in their recruitment to memory circuits.

    • Vladimir Jovasevic
    • , Elizabeth M. Wood
    •  & Jelena Radulovic

  • Article
    | Open Access

    The CIP2A–TOPBP1 complex tethers fragmented chromosomes from micronuclei for asymmetric mitotic inheritance, explaining distinct patterns of chromosome rearrangements in cancers and genomic disorders.

    • Yu-Fen Lin
    • , Qing Hu
    •  & Peter Ly

  • Article |

    Depletion of TRF2—an essential mediator of telomere protection in most mammalian cells—in mouse embryonic stem cells activates a compensatory transcriptional program that renders TRF2 dispensable for their survival and proliferation.

    • Marta Markiewicz-Potoczny
    • , Anastasia Lobanova
    •  & Eros Lazzerini Denchi

  • Article |

    Cryo-EM structures of the FANCI–FANCD2 complex bound to DNA reveal that monoubiquitination triggers structural changes that enable the complex to function as a sliding DNA clamp and coordinate the repair of DNA interstrand crosslinks.

    • Renjing Wang
    • , Shengliu Wang
    •  & Nikola P. Pavletich

  • Article |

    The structure of the multiprotein Fanconi anaemia core complex, determined using cryo-electron microscopy and mass spectrometry, shows that the complex adopts an extended asymmetric structure and highlights the structural and functional asymmetry of the RING finger domains.

    • Shabih Shakeel
    • , Eeson Rajendra
    •  & Lori A. Passmore

  • Article |

    Transcription-blocking DNA lesions result in chromatin displacement of core spliceosomes containing U2 and U5 snRNPs; consequently, R-loops containing the nascent transcript are formed, which activate ATM in a feed-forward fashion to influence spliceosome dynamics and alternative splicing.

    • Maria Tresini
    • , Daniël O. Warmerdam
    •  & Jurgen A. Marteijn

  • Article |

    KAT5 tyrosine phosphorylation, mediated by the tyrosine kinase c-Abl, increases after DNA damage, promoting KAT5 binding to histone H3K9me3, which triggers KAT5-mediated acetylation of the ATM kinase; this promotes the activation of the DNA damage checkpoint and cell survival.

    • Abderrahmane Kaidi
    •  & Stephen P. Jackson

  • Letter |

    The telomere-biding protein TRF2 is shown to protect telomeres from activating the DNA-damage response through two mechanisms: preventing the activation ATM kinase through its dimerization domain, in addition to independently suppressing signalling events occurring downstream of ATM.

    • Keiji Okamoto
    • , Cristina Bartocci
    •  & Eros Lazzerini Denchi

  • Article |

    The presence of DNA lesions is a clear signal that initiates the DNA damage response; however, the mechanisms that attenuate this response when repair has occurred are less clear. Here, deacetylation of Sae2 by Rpd3 and Hda1 is shown to be required for it to act on Mre11. When the role of Sae2 in resection is completed, it is acetylated by Gcn5 and degraded through an autophagic pathway. This work highlights links between DNA damage signalling, acetylation of repair factors, and autophagy mediated degradation of these factors.

    • Thomas Robert
    • , Fabio Vanoli
    •  & Marco Foiani

  • 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 |

    Here it is shown that reactivation of endogenous telomerase activity in mice extends telomeres, reduces DNA damage signalling, allows resumption of proliferation in quiescent cultures, and eliminates degenerative phenotypes across multiple organs including testes, spleens and intestines. Accumulating evidence implicating telomere damage as a driver of age-associated organ decline and disease and the reversal of damage observed here support the development of regenerative strategies designed to restore telomere integrity.

    • Mariela Jaskelioff
    • , Florian L. Muller
    •  & Ronald A. DePinho

  • Letter |

    The ends of chromosomes, known as telomeres, look like ends generated by double-strand breaks, but if treated as such the DNA damage repair system would initiate a checkpoint response and cause telomere–telomere fusions. These authors show that telomeres lack two types of histone modification that are required for recruitment of Crb2b53BP1, without which the checkpoint cannot be activated even if other DNA damage response proteins are recruited to a Taz1-deficient telomere.

    • Tiago Carneiro
    • , Lyne Khair
    •  & Miguel Godinho Ferreira

  • Letter |

    Cell cycle checkpoints, such as the S-phase checkpoint, delay cell division to give the cell time to repair any damaged DNA. Here it is shown that the MLL gene — frequently disrupted in leukaemia — is part of the S-phase checkpoint. When DNA is damaged, MLL is phosphorylated by the ATR protein, causing MLL to accumulate on chromatin and methylate histone H3 on lysine 4. This delays DNA replication. MLL translocations, such as those that occur in leukaemia, disrupt this pathway and cause genomic instability.

    • Han Liu
    • , Shugaku Takeda
    •  & James J.-D. Hsieh

  • 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

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