DNA damage response articles within Nature Communications

Featured

• Article
  08 April 2024 | Open Access

  p53 promotes revival stem cells in the regenerating intestine after severe radiation injury

  The tumor suppressor p53 is the guardian of the genome. Here, the authors use comprehensive approaches to demonstrate that transient p53 activity induces revival stem cells to promote the regeneration of severely irradiated intestinal epithelium in mice.

  • Clara Morral
  • , Arshad Ayyaz
  •  & David G. Kirsch

• Article
  02 April 2024 | Open Access

  PARP2 promotes Break Induced Replication-mediated telomere fragility in response to replication stress

  Here the authors show that PARP2 drives telomere fragility by orchestrating the Break-induced replication (BIR) pathway. This promotes DNA end resection and DNA synthesis via the regulation of POLD3.

  • Daniela Muoio
  • , Natalie Laspata
  •  & Elise Fouquerel

• Article
  28 March 2024 | Open Access

  Mitochondrial H₂O₂ release does not directly cause damage to chromosomal DNA

  Nuclear DNA damage downstream of mitochondrial ROS is often cited to contribute to cancer initiation and aging. However, here the authors show that although H₂O₂ induces DNA mutations when produced near DNA, it does not when released by mitochondria.

  • Daan M. K. van Soest
  • , Paulien E. Polderman
  •  & Tobias B. Dansen

• Article
  12 March 2024 | Open Access

  ZNF827 is a single-stranded DNA binding protein that regulates the ATR-CHK1 DNA damage response pathway

  Here, the authors characterise the zinc finger protein ZNF827 as a single stranded DNA binding protein that accumulates at stalled replication forks to activate the ATR-CHK1 pathway and engage homologous-recombination mediated DNA repair.

  • Sile F. Yang
  • , Christopher B. Nelson
  •  & Hilda A. Pickett

• Article
  08 March 2024 | Open Access

  GRB2 stabilizes RAD51 at reversed replication forks suppressing genomic instability and innate immunity against cancer

  GRB2 is known for its role in Receptor Tyrosine Kinase and RAS signaling. Here the authors unveil a GRB2 function and mechanism for DNA replication fork protection. GRB2 alleviates oncogenic replication stress, and in doing so, averts cancer immune destruction by inhibiting cGAS/STING and pro-inflammatory cytokine production.

  • Zu Ye
  • , Shengfeng Xu
  •  & Zamal Ahmed

• Article
  29 February 2024 | Open Access

  The Deinococcus protease PprI senses DNA damage by directly interacting with single-stranded DNA

  Lu et al. show that single-stranded DNA produced as a result of DNA damage may directly activate PprI in Deinococcus species, triggering the DNA damage response.

  • Huizhi Lu
  • , Zijing Chen
  •  & Yuejin Hua

• Article
  21 February 2024 | Open Access

  Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair

  Aberrant expression of Synaptonemal complex protein 2 (SYCP2) in breast and ovarian cancers is associated with resistance to drugs targeting the DNA damage response. Here the authors show that SYCP2 confers drug resistance by promoting R-loop formation during transcription-coupled homologous recombination.

  • Yumin Wang
  • , Boya Gao
  •  & Li Lan

• Article
  12 December 2023 | Open Access

  Nuclear cGAS restricts L1 retrotransposition by promoting TRIM41-mediated ORF2p ubiquitination and degradation

  Zhen and colleagues show that nuclear cGAS represses L1 retrotransposition to stabilize the genome by enhancing the interaction between ORF2p and the E3 ligase TRIM41 upon DNA damage, which leads to the ubiquitination and degradation of ORF2p.

  • Zhengyi Zhen
  • , Yu Chen
  •  & Zhiyong Mao

• Article
  28 November 2023 | Open Access

  Nuclear actin polymerization rapidly mediates replication fork remodeling upon stress by limiting PrimPol activity

  How nuclear architecture assists the replication stress response is still largely unknown. Here the authors show that nuclear actin polymerization rapidly extends upon mild DNA damage. By limiting Primpol activity, this response mediates fork slowing and reversal, protecting chromosome stability.

  • Maria Dilia Palumbieri
  • , Chiara Merigliano
  •  & Massimo Lopes

• Article
  22 November 2023 | Open Access

  A dual role of RBM42 in modulating splicing and translation of CDKN1A/p21 during DNA damage response

  Here the authors show a function of RBM42 in regulating splicing and translation of the p53-target gene CDKN1A/p21. This makes RBM42 an RNA-binding protein that links splicing and translation to fine-tune gene expression during DNA damage.

  • Bella M. Ben-Oz
  • , Feras E. Machour
  •  & Nabieh Ayoub

• Article
  21 November 2023 | Open Access

  Reduced FOXF1 links unrepaired DNA damage to pulmonary arterial hypertension

  It is unknown whether unrepaired DNA damage in lung endothelial cells causes persistent pulmonary arterial hypertension. Here, the authors combine oxidative stress with impaired BMPR2 signaling to link a reduction in FOXF1 to unrepaired DNA damage and impaired regeneration of normal endothelium.

  • Sarasa Isobe
  • , Ramesh V. Nair
  •  & Marlene Rabinovitch

• Article
  04 November 2023 | Open Access

  Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs

  ALT cells use an alternative lengthening mechanism of telomeres and bear telomeric DNA damage with increased levels of damage-induced long non-coding RNA. Here the AUs show that antisense oligonucleotides (ASO) targeting such RNAs can induce ALT cancer cells selective cell death.

  • Ilaria Rosso
  • , Corey Jones-Weinert
  •  & Fabrizio d’Adda di Fagagna

• Article
  30 September 2023 | Open Access

  The RNA m5C modification in R-loops as an off switch of Alt-NHEJ

  Here the authors show that DNA damage induced RNA m5C in R-loops competes with PARP1- mediated PARylation in transcribed genomes to promote cell survival which could be targeted be in cancer therapy.

  • Haibo Yang
  • , Emily M. Lachtara
  •  & Li Lan

• Article
  22 September 2023 | Open Access

  SENP6 regulates localization and nuclear condensation of DNA damage response proteins by group deSUMOylation

  The authors show that the SUMO protease SENP6 plays an essential role in maintaining genome integrity by disassembling SUMO2/3 polymers from DNA damage response proteins, thereby preventing their trapping at sites of DNA damage and in nuclear condensates.

  • Laura A. Claessens
  • , Matty Verlaan-de Vries
  •  & Alfred C. O. Vertegaal

• Article
  25 August 2023 | Open Access

  A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells

  Here the authors study how BRCA2 mutations affect mammary epithelial subpopulations. They report that Brca2^mut/WT mammary organoids subjected to replication stress activate a transcriptional response that selectively expands Brca2^mut/WT HR- luminal cells.

  • Maryam Ghaderi Najafabadi
  • , G. Kenneth Gray
  •  & Mona Shehata

• Article
  22 August 2023 | Open Access

  Histone H3 serine-57 is a CHK1 substrate whose phosphorylation affects DNA repair

  Histone post-translational modifications control several fundamental processes on DNA. Here, the authors describe a conserved phosphorylation of histone H3 on the globular core and show that it loosens the nucleosome and regulates DNA repair.

  • Nikolaos Parisis
  • , Pablo D. Dans
  •  & Daniel Fisher

• Article
  18 July 2023 | Open Access

  Regulation of Rad52-dependent replication fork recovery through serine ADP-ribosylation of PolD3

  Here the authors identify that PARP1 maintains genome integrity by regulating replication fork recovery by break-induced replication. Mechanistically, this is achieved through MRE11-dependent PARP1 activation and site-specific ADP-ribosylation of PolD3.

  • Frederick Richards
  • , Marta J. Llorca-Cardenosa
  •  & Nicholas D. Lakin

• Article
  10 July 2023 | Open Access

  Cell cycle arrest and p53 prevent ON-target megabase-scale rearrangements induced by CRISPR-Cas9

  ON-target genotoxicity in gene editing is generally underestimated. Here the authors report Fluorescence-Assisted Megabase-scale Rearrangements Detection (FAMReD) systems to detect and characterize rare large loss of heterozygosity: they show that ON-target genotoxicity can be prevented by p53 and cell cycle arrest.

  • G. Cullot
  • , J. Boutin
  •  & A. Bedel

• Article
  02 June 2023 | Open Access

  Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling

  In the DNA damage response, ADP-ribosylation is an essential signaling pathway. Here the authors utilize a multidisciplinary approach to establish its molecular basis in fruit flies and provide evidence for Drosophila’s suitability as model organism.

  • Pietro Fontana
  • , Sara C. Buch-Larsen
  •  & Ivan Ahel

• Article
  20 April 2023 | Open Access

  Integrated transcriptome landscape of ALS identifies genome instability linked to TDP-43 pathology

  The causes of ALS remain unclear with many proposed pathomechanisms. Here, the authors integrate iPSC-derived motor neuron and post-mortem datasets and identify a heightened DNA damage response accompanied by accumulation of somatic mutations in ALS.

  • Oliver J. Ziff
  • , Jacob Neeves
  •  & Rickie Patani

• Article
  02 February 2023 | Open Access

  Antecedent chromatin organization determines cGAS recruitment to ruptured micronuclei

  DNA damage-induced micronuclei are linked to downstream viral signalling through the cGAS pattern recognition receptor. Here, the authors identify features of micronuclei chromatin that determine cGAS-MN recruitment and associated pathway activation.

  • Kate M. MacDonald
  • , Shirony Nicholson-Puthenveedu
  •  & Shane M. Harding

• Article
  26 December 2022 | Open Access

  Arabidopsis γ-H2A.X-INTERACTING PROTEIN participates in DNA damage response and safeguards chromatin stability

  γ-H2A.X is a critical signal for DNA double strand break responses. In this study, an Arabidopsis protein that interacts with γ-H2A.X and the recombinase RAD51 is shown to contribute to plant chromatin stability and integrity.

  • Tianyi Fan
  • , Huijia Kang
  •  & Yan Zhu

• Article
  08 November 2022 | Open Access

  Regulation of BRCA1 stability through the tandem UBX domains of isoleucyl-tRNA synthetase 1

  Aminoacyl-tRNA synthetases possess unique domains. In this study the structure of the vertebrate IARS1 and EARS1 complex reveals that vertebrate IARS1 protects the DNA repair factor BRCA1 from proteolytic degradation via its UBX-fold domain.

  • Scisung Chung
  • , Mi-Sun Kang
  •  & Yunje Cho

• Article
  20 October 2022 | Open Access

  A BDNF-TrkB autocrine loop enhances senescent cell viability

  Selective elimination of senescent cells is an approach that has shown promise to ameliorate age-associated pathologies in preclinical models. Here the authors report that BDNF enhances senescent cell viability via TrkB in cultured cells, and that TrkB inhibition can reduce the accumulation of senescent cells in aged mouse organs.

  • Carlos Anerillas
  • , Allison B. Herman
  •  & Myriam Gorospe

• Article
  10 October 2022 | Open Access

  ISG15 conjugation to proteins on nascent DNA mitigates DNA replication stress

  DNA replication stress can result in genome instability. Here the authors show that the ubiquitin like modifier protein, ISG15, important during the innate immune response, acts at replication forks to mitigate DNA replication stress.

  • Christopher P. Wardlaw
  •  & John H. J. Petrini

• Article
  02 October 2022 | Open Access

  XPF activates break-induced telomere synthesis

  Here the authors show TERRA R-loops recruit the endonuclease XPF to telomeres, leading to DNA double-strand breaks to activate break-induced telomere synthesis at telomeres that utilize the alternative lengthening of telomeres (ALT) pathway to extend their telomeres independent of telomerase.

  • Chia-Yu Guh
  • , Hong-Jhih Shen
  •  & Hsueh-Ping Catherine Chu

• Article
  01 August 2022 | Open Access

  ROR2 regulates self-renewal and maintenance of hair follicle stem cells

  Wnt signaling functions in tissue homeostasis and tumorigenesis. Here the authors show that ROR2, a Wnt receptor, plays roles not only in transducing Wnt signaling, but also in regulation of DNA damage response critical for stem cell maintenance.

  • Anthony Veltri
  • , Christopher M. R. Lang
  •  & Wen-Hui Lien

• Article
  22 July 2022 | Open Access

  TDP1-independent pathways in the process and repair of TOP1-induced DNA damage

  Here the authors find that MUS81 mediates excess DNA double strand break (DSB) generation in TDP1 KO cells after camptothecin treatment. They show that TOP1 cleavage complexes can be either resolved directly by TDP1 or be converted into DSBs and repaired further by the Homologous Recombination pathway.

  • Huimin Zhang
  • , Yun Xiong
  •  & Junjie Chen

• Article
  24 June 2022 | Open Access

  DNA damage-induced transcription stress triggers the genome-wide degradation of promoter-bound Pol II

  DNA damage inhibits elongating RNA polymerase II, but also initiates genome-wide transcriptional responses. Here the authors reveal that particularly promoter-bound Pol II is degraded upon DNA damage in a GSK3 signaling-mediated response.

  • Barbara Steurer
  • , Roel C. Janssens
  •  & Jurgen Marteijn

• Article
  04 November 2021 | Open Access

  SPINDOC binds PARP1 to facilitate PARylation

  SPINDOC is known to interact with Spindlin1 (SPIN1), a histone code effector protein. Here, the authors show that SPINDOC is distributed between two distinct protein complexes, one comprising SPIN1 and the other one with PARP1. Their results suggest a role for SPINDOC in the regulation of PARP1- mediated PARylation and the DNA damage response.

  • Fen Yang
  • , Jianji Chen
  •  & Mark T. Bedford

• Article
  17 September 2021 | Open Access

  Distinct functions of POT1 proteins contribute to the regulation of telomerase recruitment to telomeres

  Mammalian shelterin proteins POT1 and TPP1 form a stable heterodimer that protects telomere ends. The authors exploit the observation that mice have two POT1 paralogs, enabling functional dissections to shed important light on the mechanistic basis for human POT1 functions.

  • Peili Gu
  • , Shuting Jia
  •  & Sandy Chang

• Article
  01 July 2021 | Open Access

  Serine-linked PARP1 auto-modification controls PARP inhibitor response

  PARP inhibitors function by trapping PARP1 protein on DNA breaks, which has cytotoxic consequences to cancer cells. Here the authors identify three serine residues within PARP1 as key sites whose efficient HPF1-dependent modification counters PARP1 trapping and contributes to inhibitor tolerance.

  • Evgeniia Prokhorova
  • , Florian Zobel
  •  & Ivan Ahel

• Article
  22 June 2021 | Open Access

  RPA shields inherited DNA lesions for post-mitotic DNA synthesis

  Single-stranded DNA during DNA replication and repair in S/G2 needs protection by replication protein A (RPA). Here the authors reveal that RPA also shields inherited single-stranded DNA in G1, representing replication remnants from the previous cell cycle, to allow for post-mitotic DNA synthesis.

  • Aleksandra Lezaja
  • , Andreas Panagopoulos
  •  & Matthias Altmeyer

• Article
  05 May 2021 | Open Access

  The lncRNA Caren antagonizes heart failure by inactivating DNA damage response and activating mitochondrial biogenesis

  Long noncoding RNAs (lncRNAs) have been shown to play a role in cardiac physiology and disease. Here the authors identify the lncRNA Caren as a cytoplasmic RNA that decreases the translation of a distant gene encoding Hint1, thereby maintaining cardiomyocyte function due to inactivation of the DNA damage response and activation of mitochondrial bioenergetics.

  • Michio Sato
  • , Tsuyoshi Kadomatsu
  •  & Yuichi Oike

• Article
  23 February 2021 | Open Access

  A synergetic effect of BARD1 mutations on tumorigenesis

  Mutations in the BARD1 gene have been identified as risk factors in breast and ovarian cancers. Here the authors reveal a synergetic effect between the occurance of two cis mutations in the BARD1 gene affecting the cellular DNA damage response and consequently tumorigenesis.

  • Wenjing Li
  • , Xiaoyang Gu
  •  & Mo Li

• Article
  15 February 2021 | Open Access

  HPF1 remodels the active site of PARP1 to enable the serine ADP-ribosylation of histones

  Once DNA breaks occur, poly(ADP-ribose) polymerase 1 (PARP1) ADP-ribosylates itself and other DNA repair factors to initiate the repair process. Here, the authors resolve the crystal structures of mouse and human HPF1, and human HPF1/PARP1 complex proving insights into PARP1 regulation.

  • Fa-Hui Sun
  • , Peng Zhao
  •  & Cai-Hong Yun

• Article
  20 January 2021 | Open Access

  Endonuclease G promotes autophagy by suppressing mTOR signaling and activating the DNA damage response

  The role of Endonuclease G in autophagy remains unclear. Here the authors report that ENDOG is released from mitochondria during starvation and promotes autophagy by suppressing mTOR signaling and activating DNA damage response.

  • Wenjun Wang
  • , Jianshuang Li
  •  & Qinghua Zhou

• Article
  13 November 2020 | Open Access

  CHD7 and 53BP1 regulate distinct pathways for the re-ligation of DNA double-strand breaks

  Chromatin is dynamically remodeled in response to DNA damage in favour of repair. Here the authors reveal how the chromatin remodeler CHD7 and chromatin binding protein 53BP1 regulate distinct DNA repair pathways.

  • Magdalena B. Rother
  • , Stefania Pellegrino
  •  & Haico van Attikum

• Article
  03 November 2020 | Open Access

  The HUSH complex is a gatekeeper of type I interferon through epigenetic regulation of LINE-1s

  The HUSH complex has been implicated in repressing LINE-1 elements. Here the authors reveal that the complex negatively regulates the type I IFN response in human cells through epigenetic regulation of LINE-1 elements

  • Hale Tunbak
  • , Rocio Enriquez-Gasca
  •  & Helen M. Rowe

• Article
  30 October 2020 | Open Access

  SDE2 integrates into the TIMELESS-TIPIN complex to protect stalled replication forks

  The fork protection complex (FPC), including the proteins TIMELESS and TIPIN, stabilizes the replisome to ensure unperturbed fork progression during DNA replication. Here the authors reveal that that SDE2, a PCNA-associated protein, plays an important role in maintaining active replication and protecting stalled forks by regulating the replication fork protection complex (FPC).

  • Julie Rageul
  • , Jennifer J. Park
  •  & Hyungjin Kim

• Article
  18 May 2020 | Open Access

  Histone H2A variants alpha1-extension helix directs RNF168-mediated ubiquitination

  Histone ubiquitination plays a critical role in the DNA damage response pathway. Here the authors reveal how RNF168 ubiquitinates the H2A family including noncanonical variants, H2AZ and macroH2A1/2, at the divergent N-terminal tail lysine residue.

  • Jessica L. Kelliher
  • , Kirk L. West
  •  & Justin W. C. Leung

• Article
  14 May 2020 | Open Access

  Genotoxic stress triggers the activation of IRE1α-dependent RNA decay to modulate the DNA damage response

  IRE1α plays a key role in the unfolded protein response (UPR) by promoting the unconventional splicing of the XBP1 and the selective cleavage of RNAs. Here the authors report that IRE1α is activated upon the DNA damage response and selectively controls the stability of mRNAs to maintain genome integrity.

  • Estefanie Dufey
  • , José Manuel Bravo-San Pedro
  •  & Claudio Hetz

• Article
  01 May 2020 | Open Access

  Real-time monitoring of PARP1-dependent PARylation by ATR-FTIR spectroscopy

  The mechanism of PARP1-dependent poly-ADP-ribosylation in response to DNA damage is still under debate. Here, the authors use ATR-FTIR spectroscopy to provide time-resolved insights into the molecular details of this process under near physiological conditions.

  • Annika Krüger
  • , Alexander Bürkle
  •  & Aswin Mangerich

• Article
  29 April 2020 | Open Access

  Structural basis for DNA damage-induced phosphoregulation of MDM2 RING domain

  p53 is an important tumor suppressor protein which is regulated by the E3 ubiquitin ligase MDM2. Here the authors reveal that DNA damage-induced Ser429 phosphorylation of MDM2 serve to boost the activity of MDM2 homodimer by stabilizing the active E2–ubiquitin complex and promote its self-destruction to enable rapid p53 stabilization.

  • Helge M. Magnussen
  • , Syed F. Ahmed
  •  & Danny T. Huang

• Article
  14 February 2020 | Open Access

  Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency

  The ATM kinase is a key regulator of the DNA damage response to double-strand breaks (DSBs) and its homozygous loss in patients predisposes to lymphoid malignancies. Here, the authors develop a Tdp2^−/− Atm^−/− double-deficient mouse model to uncover topoisomerase II-induced DSBs as significant drivers of the genomic rearrangements that underpin these tumours.

  • Alejandro Álvarez-Quilón
  • , José Terrón-Bautista
  •  & Felipe Cortés-Ledesma

• Article
  16 December 2019 | Open Access

  ATAD5 promotes replication restart by regulating RAD51 and PCNA in response to replication stress

  How the replisome machinery contributes to fork stability under replication stress is currently not clear. Here the authors reveal a role for ATAD5 in maintaining genome integrity during replication stress by promoting replication restart through RAD51/PCNA regulation.

  • Su Hyung Park
  • , Nalae Kang
  •  & Kyungjae Myung

• Article
  24 October 2019 | Open Access

  Occurrence and repair of alkylating stress in the intracellular pathogen Brucella abortus

  It is assumed that intracellular pathogenic bacteria must cope with DNA alkylating stress within host cells. Here, Poncin et al. show that the pathogen Brucella abortus does encounter alkylating stress within macrophages, and shed light into the pathways required for DNA repair in this organism.

  • Katy Poncin
  • , Agnès Roba
  •  & Xavier De Bolle

• Article
  11 October 2019 | Open Access

  Structure and functional implications of WYL domain-containing bacterial DNA damage response regulator PafBC

  The transcriptional activator PafBC is a regulator of mycobacterial DNA damage response and upregulates genes involved in DNA repair. Here, the authors present the crystal structure of Arthrobacter aurescens PafBC and suggest that PafBC might be activated by binding of a nucleic acid ligand, and bioinformatics analysis shows that its central WYL domain is a widespread feature in bacterial transcription factors.

  • Andreas U. Müller
  • , Marc Leibundgut
  •  & Eilika Weber-Ban

• Article
  23 August 2019 | Open Access

  hCINAP regulates the DNA-damage response and mediates the resistance of acute myelocytic leukemia cells to therapy

  Acute myeloid leukemia cells are often resistant to radiotherapy and chemotherapy. Here, the authors suggest that hCINAP contributes to the resistance of acute myeloid leukemia cells by regulating SUMOylation of Nucleophosmin during the DNA-damage response.

  • Ruidan Xu
  • , Shuyu Yu
  •  & Xiaofeng Zheng

• Article
  22 July 2019 | Open Access

  Identification of intracellular cavin target proteins reveals cavin-PP1alpha interactions regulate apoptosis

  Caveolae are plasma membrane invaginations containing cavin proteins that are disrupted upon stress stimuli, causing cavin release inside the cell. Here, McMahon et al. identify cavin interacting proteins using proteomic analyses and reveal functions in stress signaling that can promote apoptosis.

  • Kerrie-Ann McMahon
  • , Yeping Wu
  •  & Robert G. Parton